Search

Key Points: Question: Is systemic oxidative stress-induced damage to RNA and DNA increased in community-dwelling individuals with psychiatric illness and associated with all-cause mortality? Findings: In this cohort study, oxidative stress-induced damage to RNA was increased in individuals with psychiatric illness and showed a dose-response association with mortality. Meaning: The findings suggest that RNA damage from oxidation may be a mechanism in the accelerated aging observed in psychiatric illness and could have utility as a marker of mortality risk in these common disorders. This cohort study evaluates the association between oxidative stress on nucleic acids and all-cause mortality in individuals with and without psychiatric illness. Importance: All-cause mortality and the risk for age-related medical disease is increased in individuals with psychiatric illness, but the underlying biological mechanisms are not known. Oxidative stress on nucleic acids (DNA and RNA; NA-OXS) is a molecular driver of aging and a potential pathophysiological mechanism in a range of age-related disorders. Objective: To study the levels of markers of NA-OXS in a large cohort of community-dwelling individuals with and without psychiatric illness and to evaluate their association with prospective all-cause mortality. Design, Setting, and Participants: This cohort study used a combined cohort of participants from 2 population-based health studies: the Danish General Suburban Population Study (January 2010 to October 2013) and nondiabetic control participants from the Vejle Diabetes Biobank study (March 2007 to May 2010). Individual history of psychiatric illness was characterized using register data on psychiatric diagnoses and use of psychotropic drugs before baseline examination. Urinary markers of systemic RNA (8-oxo-7,8-dihydroguanosine [8-oxoGuo]) and DNA (8-oxo-7,8-dihydro-2'-deoxyguanosine [8-oxodG]) damage from oxidation were measured by ultraperformance liquid chromatography–tandem mass spectrometry. Cox proportional hazard regression models were applied for survival analyses, using register-based all-cause mortality updated to May 2023. The follow-up time was up to 16.0 years. Exposures: History of psychiatric illness. Main Outcomes and Measures: Mortality risk according to psychiatric illness status and 8-oxoGuo or 8-oxodG excretion level. Results: A total of 7728 individuals were included (3983 [51.5%] female; mean [SD] age, 58.6 [11.9] years), 3095 of whom (40.0%) had a history of psychiatric illness. Mean (SD) baseline 8-oxoGuo was statistically significantly higher in individuals with psychiatric illness than in those without (2.4 [1.2] nmol/mmol vs 2.2 [0.9] nmol/mmol; P <.001), whereas 8-oxodG was not. All-cause mortality was higher in the psychiatric illness group vs the no psychiatric illness group (hazard ratio [HR], 1.44; 95% CI, 1.27-1.64; P <.001) and increased sequentially with each increasing tertile of 8-oxoGuo excretion in both groups to an almost doubled risk in the psychiatric illness/high 8-oxoGuo group compared to the no psychiatric illness/low 8-oxoGuo reference group (HR, 1.99; 95% CI, 1.58-2.52; P <.001). These results persisted after adjustment for a range of potential confounders and in a sensitivity analysis stratified for sex. Conclusions and Relevance: This study establishes systemic oxidative stress-induced damage to RNA as a potential mechanism in the accelerated aging observed in psychiatric disorders and urinary 8-oxoGuo as a potentially useful marker of mortality risk in individuals with psychiatric illness. [ABSTRACT FROM AUTHOR]

• DNA recovered from regularly-worn jumpers before and after use by a second wearer. • When worn by one wearer, most samples gave major or single-source profile of wearer. • After second wearer, reproducible profile compositions varied between pairings. • Shedder status affected DNA quantities and profile compositions between wearers. • Neither recovery method nor sampling location impacted DNA profile composition. Items of worn clothing are routinely examined for DNA in forensic casework, commonly with the expectation that at least some of the DNA will come from a wearer of the item, so-called 'wearer DNA'. This study investigated DNA recovered from hooded jumpers that were regularly worn and laundered for four weeks and then subsequently worn by a different individual for four hours. This study also systematically investigated whether using different recovery methods or sampling locations on the jumpers might distinguish between DNA deposited by the regular and most recent wearers of clothing. Four volunteers each wore a new hooded jumper regularly (6 h/day, 2 days/week, washed at weekends) during two 4-week periods. At the end of each month, DNA was first recovered by cutting out and mini-taping the inside left cuff, half-collar, pocket and underarm fabric. The jumpers were then worn by a different individual for four hours, and DNA was again recovered by cutting out and mini-taping, but this time from the inside right cuff, half-collar, pocket and underarm fabric. All DNA samples (n = 128) were quantified and profiled. DNA quantities ranged from 0 to ∼40 ng with an outlier of ∼150 ng, and no significant differences were observed among recovery methods and sampling locations, nor whether one or two wearers had worn the jumpers. However, one volunteer consistently deposited significantly more DNA to their jumpers than two other volunteers, confirming the impact of 'shedder status' on DNA deposition during wearing of clothing. When jumpers were regularly worn by one wearer, the majority (72.7–83.3 %) of the samples for all wearers across both months comprised a major profile of the wearer with a minor profile of non-wearer alleles. When jumpers were then worn by a second wearer, the composition of the profiles obtained were generally reproducible across the recovery methods used, the sampling locations and the two replicates of the experiment for each pairing of wearers. However, profile compositions differed between wearer pairings. Overall, ∼60 % of profiles obtained gave a major profile of the regular wearer, whereas ∼30 % gave a major profile of the second wearer. The remaining profiles comprised other much less frequent observations of single-source profiles of each wearer and equal proportions of DNA from both wearers. Non-wearer DNA was also observed in the majority of samples, both before and after jumpers were worn by a second wearer. For one volunteer's jumpers, a recurring non-wearer DNA profile was observed that could be attributed to their romantic partner, and this DNA persisted on the jumpers even after being worn by the second wearer. This study provides insight on the impact of shedder status, multiple wearers, different recovery methods and sampling locations on the quantities of DNA and compositions of DNA profiles recovered from authentically regularly-worn hooded jumpers. The findings also provide a preliminary dataset that can be used to infer activity level probabilities in casework. [ABSTRACT FROM AUTHOR]

Macroautophagy (referred to as autophagy hereafter) is a major intracellular lysosomal degradation pathway that is responsible for the degradation of misfolded/damaged proteins and organelles. Previous studies showed that autophagy protects against acetaminophen (APAP)-induced injury (AILI) via selective removal of damaged mitochondria and APAP protein adducts. The lysosome is a critical organelle sitting at the end stage of autophagy for autophagic degradation via fusion with autophagosomes. In the present study, we showed that transcription factor EB (TFEB), a master transcription factor for lysosomal biogenesis, was impaired by APAP resulting in decreased lysosomal biogenesis in mouse livers. Genetic loss-of and gain-of function of hepatic TFEB exacerbated or protected against AILI, respectively. Mechanistically, overexpression of TFEB increased clearance of APAP protein adducts and mitochondria biogenesis as well as SQSTM1/p62-dependent non-canonical nuclear factor erythroid 2-related factor 2 (NRF2) activation to protect against AILI. We also performed an unbiased cell-based imaging high-throughput chemical screening on TFEB and identified a group of TFEB agonists. Among these agonists, salinomycin, an anticoccidial and antibacterial agent, activated TFEB and protected against AILI in mice. In conclusion, genetic and pharmacological activating TFEB may be a promising approach for protecting against AILI. Genetic and pharmacological activation of TFEB increases lysosomal biogenesis that promotes clearance of acetaminophen adducts resulting in protection against AILI. qHTS is a very useful platform to identify novel mTOR-dependent and independent TFEB agonists that may have translational therapeutic value for targeting drug-induced liver injury. [Display omitted] [ABSTRACT FROM AUTHOR]

Scientific evidence about genetic and molecular changes in oral squamous cell carcinoma (OSCC) among smokers and non-smokers is inconclusive. This systematic review and meta-analysis assessed the effects of tobacco on the DNA of individuals with OSCC based on protein mutations. Electronic searches were conducted on PubMed, Ovid, Web of Science, and Scopus to identify observational studies published up to January/2022. The Joanna Briggs Institute tool was used for the critical appraisal of studies. The certainty of the evidence was evaluated. Twenty-three studies assessing 4,060 individuals (2,967 smokers vs. 1,093 non-smokers) were included in this review. Fifteen groups of proteins/genes were investigated. Analysis of the quality of articles revealed low risk of bias in most studies. The certainty of the evidence was very low. The meta-analysis confirmed no significant difference between smokers and non-smokers with respect to damage to GSTM1 (OR: 0.60; 95%CI: 0.30-1.18), GSTT1 (OR: 1.18; 95%CI:0.49-2.83), hydrolase proteins (Ku70 and Ku80) (OR: 0.74; 95%CI: 0.18-3.05), and transferase proteins (GSTM1, GSTT1, GSTM3) (OR: 0.74; 95%CI: 0.47-1.18). Most of the studies included showed that smokers are more likely to exhibit genetic instability. However, the meta-analysis revealed that smokers do not necessarily have more genetic alterations in the DNA than non-smokers. [ABSTRACT FROM AUTHOR]

Cigarette smoke, a complex mixture produced by tobacco combustion, contains a variety of carcinogens and can trigger DNA damage. Overactivation of c-MET, a receptor tyrosine kinase, may cause cancer and cellular DNA damage, but the underlying mechanisms are unknown. In this work, we investigated the mechanisms of cigarette smoke extract (CSE) induced malignant transformation and DNA damage in human bronchial epithelial cells (BEAS-2B). The results demonstrated that CSE treatment led to up-regulated mRNA expression of genes associated with the c-MET signaling pathway, increased expression of the DNA damage sensor protein γ-H2AX, and uncontrolled proliferation in BEAS-2B cells. ATR, ATR, and CHK2, which are involved in DNA damage repair, as well as the phosphorylation of c-MET and a group of kinases (ATM, ATR, CHK1, CHK2) involved in the DNA damage response were all activated by CSE. In addition, CSE activation promotes the phosphorylation modification of ATR, CHK1 proteins associated with DNA damage repair. The addition of PHA665752, a specific inhibitor of c-MET, or knock-down with c-MET both attenuated DNA damage, while overexpression of c-MET exacerbated DNA damage. Thus, c-MET phosphorylation may be involved in CSE-induced DNA damage, providing a potential target for intervention in the prevention and treatment of smoking-induced lung diseases. • CSE triggers DNA damage and malignant transformation in human bronchial epithelial cells. • c-MET phosphorylation and DNA damage response are activated by CSE. • c-MET phosphorylation mediates CSE-induced DNA damage. [ABSTRACT FROM AUTHOR]

Urban outdoor workers (OWs), identified as professionals spending most of their working shifts in an urban environment, are exposed for at least 8 h/day to traffic air pollution, leading to potential health risks. This paper reports the results of a systematic review aimed at identifying the potential health outcomes of exposure to air pollutants for OWs, focusing mainly on police officers, drivers and street vendors. Health outcomes were analysed in terms of early biological effects quantified with specific measured indicators. The main inclusion criterion was the assessment of at least one early biological effect (genetic and epigenetic damage/alterations, inflammation or oxidative stress indicators, or hormonal imbalance) in a population of OWs exposed to urban air pollution. By applying the PRISMA workflow, 82 papers were included in this study. The results showed that the measured pollutant concentrations were significantly below the current occupational limit values, while exceeds the indications of WHO for urban air pollution. This exposure led to significant alterations of biological markers in OWs with respect to non-exposed subjects. In particular, OWs presented an increased frequency of micronuclei and DNA adducts as the main DNA alterations, while police officers (a category of highly exposed OWs) showed hormonal alterations affecting mainly the hypothalamic-pituitary-gonadal axis. Concerning oxidative stress and inflammation, all the analysed matrices (i.e. blood, sputum, urine and lachrymal fluids) showed increased indices for OWs respect to non-exposed groups. Therefore, the evaluation of effect biomarkers to detect early alterations provides crucial information for supporting the occupational risk management of OWs and, at broader level, allows for an insight of the early-stage health outcomes due to urban air pollution. [Display omitted] • Prolonged exposure to low doses of urban air pollutants alters early biomarkers in outdoor workers. • Outdoor workers exposure is below Occupational Exposure Limits but exceeds WHO indications. • Increased frequency of micronuclei and DNA adducts were the main DNA alterations. • All biological matrices showed increased inflammation and oxidative stress markers. • The main hormonal alterations affected the HPG axis in police officers. [ABSTRACT FROM AUTHOR]

Urbanization has numerous benefits to human society, but some aspects of urban environments, such as air pollution, can negatively affect human health. Two major air pollutants, particulate matter (PM) and polycyclic aromatic hydrocarbons (PAH), have been classified as carcinogens by the International Agency for Research on Cancer. Here, we answer two questions: (1) What are the carcinogenic effects of PM and PAH exposure? (2) How does carcinogenic risk vary across geographical regions? We performed a comprehensive literature search of peer-reviewed published studies examining the link between air pollution and human cancer rates. Focusing on studies published since 2014 when the last IARC monograph on air pollution was published, we converted the extracted data into relative risks and performed subgroup analyses. Exposure to PM 2.5 (per 10 μg/m3) resulted in an 8.5% increase in cancer incidence when all cancer types were combined, and risk for individual cancer types (i.e. lung cancer and adenocarcinoma) was also elevated. PM 2.5 was also associated with 2.5% higher mortality due to cancer when all types of cancer were combined, and for individual cancer types (i.e., lung and breast cancer). Exposure to PM 2.5 and PM 10 posed the greatest risk to lung cancer incidence and mortality in Europe (PM 2.5 RR 2.15; PM 10 RR 1.26); the risk in Asia and the Americas was also elevated. Exposure to PAH and benzo[ a ]pyrene significantly increased the pooled risk of cancer incidence (10.8% and 8.0% respectively) at the highest percentile of exposure concentration. Our meta-analyses of studies over the past decade shows that urban air pollution in the form of PM 2.5 , PM 10 , and PAH all elevate the incidence and mortality of cancer. We discuss the possible mechanisms of carcinogenesis of PM and PAH. These results support World Health Organization's conclusion that air pollution poses among the greatest health risks to humans living in cities. [Display omitted] • Novel synthesis of literature on PM & PAH exposure and cancer. • First systematic analysis of literature on PM and cancer since IARC's report in 2016 which considered studies published before 2014. • First meta-analysis to consider how PAHs affect cancer rates on general population. • PM & PAH exposure significantly increases risk of multiple forms of cancer (incidence & mortality). • Lung cancer risk (incidence & mortality) was greatest in Europe, and elevated in Asia and the Americas. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Imaging techniques based on X-ray phase-contrast (XPC) have shown tremendous promise for applications involving biomaterials and soft tissue formation. XPC imaging can be applied at higher energy offering the potential for lower dose imaging. Essential to the development of this technique and its routine use is an understanding of the potential damage of X-ray dose on cells and tissues. EXPERIMENTAL: In this study the comet assay, a sensitive assay for DNA damage, was used to evaluate DNA damage on mesenchymal stem cells (MSCs) exposed to X-ray irradiation. We examined the effects of early (immediately following irradiation) and delayed (24 h post-irradiation) X-ray effects caused by low (15 mGy) and intermediate (150 mGy and 1.5 Gy) exposure on MSCs during a monitoring period of 4 weeks (five irradiations, one weekly). Cells were submitted to a polychromatic X-ray source (Thermo Fisher PXS10 conditions: voltage 45 kV, source current 160 μA, source power 7.2 W, source spot size 9 um, photon flux on the sample 7.66 106 photons s-1mm-2 irradiation). Statistical analysis was performed by using Two-way analysis of variance (ANOVA) with Tukey’s multiple comparisons posttest in GraphPad Prism 5.0.A difference at p < 0.05 was considered statistically significant. RESULTS AND DISCUSSION: Results of the DNA comet assay indicated that early effects of low- and intermediatedose of XPC induced an increase in the number of cells with DNA damage after each irradiation, where intermediatedose (150 mGy and 1.5 Gy) produced significantly higher damage relative to controls. DNA damage induced by low and intermediate doses returned to the control value 24 h after the irradiation exposure, suggesting a strong protection of MSCs at the tested doses of XPC irradiation. CONCLUSIONS: The data presented in this study shows that 24 h after the last of five weekly low and intermediate doses XPC irradiation, the harmful effects on DNA in MSCs were not detected. The current study reinforces the need of investigating consequences of low and intermediate doses of X-ray PC irradiation in the field of tissue engineering and provide new basis for MSCs using in the clinics. [ABSTRACT FROM AUTHOR]

5-Fluorouracil (5-FU) is an anticancer drug extensively used for different cancers. Intracellular metabolic activation leads to several nucleoside and nucleotide metabolites essential to exert its cytotoxic activity on multiple cellular targets such as enzymes, DNA and RNA. In this paper, we describe the development of a method based on liquid chromatography coupled with high resolution mass spectrometry suitable for the simultaneous determination of the ten anabolic metabolites (nucleoside, nucleotide and sugar nucleotide) of 5-FU. The chromatographic separation was optimized on a porous graphitic carbon column allowing the analysis of the metabolites of 5-FU as well as endogenous nucleotides. The detection was performed on an Orbitrap® tandem mass spectrometer. Linearity of the method was verified in intracellular content and in RNA extracts. The limit of detection was equal to 12 pg injected on column for nucleoside metabolites of 5-FU and 150 pg injected on column for mono- and tri-phosphate nucleotide metabolites. Matrix effect was evaluated in cellular contents, DNA and RNA extracts for nucleoside and nucleotides metabolites. The method was successfully applied to i) measure the proportion of each anabolic metabolite of 5-FU in cellular contents, ii) follow the consequence of inhibition of enzymes on the endogenous nucleotide pools, iii) study the incorporation of metabolites of 5-FU into RNA and DNA, and iv) to determine the incorporation rate of 5-FUrd into 18 S and 28 S sub-units of rRNA. Image 1 • The LC-MS-HRMS method allows the analysis of the ten anabolic metabolites of 5-FU. • The present method is useful to study the incorporation of 5-FU into RNA and DNA. • Method to determine the incorporation rate of 5-FU into subunit of rRNA is innovative. [ABSTRACT FROM AUTHOR]

Epidemiologic studies have reported the positive relationship of benzo[ a ]pyrene (BaP) exposure with the risk of lung cancer. However, the mechanisms underlying the relationship is still unclear. Plasma microRNA (miRNA) is a typical epigenetic biomarker that was linked to environment exposure and lung cancer development. We aimed to reveal the mediation effect of plasma miRNAs on BaP-related lung cancer. We designed a lung cancer case-control study including 136 lung cancer patients and 136 controls, and measured the adducts of benzo[ a ]pyrene diol epoxide-albumin (BPDE-Alb) and sequenced miRNA profiles in plasma. The relationships between BPDE-Alb adducts, normalized miRNA levels and the risk of lung cancer were assessed by linear regression models. The mediation effects of miRNAs on BaP-related lung cancer were investigated. A total of 190 plasma miRNAs were significantly related to lung cancer status at Bonferroni adjusted P < 0.05, among which 57 miRNAs showed different levels with |fold change| > 2 between plasma samples before and after tumor resection surgery at Bonferroni adjusted P < 0.05. Especially, among the 57 lung cancer-associated miRNAs, BPDE-Alb adducts were significantly related to miR-17–3p, miR-20a-3p, miR-135a-5p, miR-374a-5p, miR-374b-5p, miR-423–5p and miR-664a-5p, which could in turn mediate a separate 42.2%, 33.0%, 57.5%, 36.4%, 48.8%, 32.5% and 38.2% of the relationship of BPDE-Alb adducts with the risk of lung cancer. Our results provide non-invasion biomarker candidates for lung cancer, and highlight miRNAs dysregulation as a potential intermediate mechanism by which BaP exposure lead to lung tumorigenesis. [Display omitted] • Lung cancer status was linked to 190 plasma miRNAs with Bonferroni adjusted P < 0.05. • 57 miRNAs further changed > 2 folds after surgery with Bonferroni adjusted P < 0.05. • Plasma BPDE-Alb adducts were related to 9 lung cancer-associated miRNAs. • 7 miRNAs mediated the association between BPDE-Alb adducts and lung cancer risk. • Plasma miRNA profiles at the epigenome level were determined. [ABSTRACT FROM AUTHOR]

Nickel is a confirmed human lung carcinogen. Nonetheless, the molecular mechanisms driving its carcinogenic impact on lung tissue remain poorly defined. In this study, we assessed SESN2 expression and the signaling pathways responsible for cellular transformation in human bronchial epithelial cells (HBECs) as a result of nickel exposure. We employed the Western blotting to determine the induction of SESN2 by nickel. To clarify the signaling pathways leading to cellular transformation following nickel exposure, we applied techniques such as gene knockdown, methylation-specific PCR, and chromatin immunoprecipitation. Exposure to nickel results in the upregulation of SESN2 and the initiation of autophagy in human bronchial epithelial cells (HBECs). This leads to degradation of HUR protein and consequently downregulation of USP28 mRNA, PP2AC protein, β-catenin protein, and diminished VHL transcription, culminating in the accumulation of hypoxia-inducible factor-1α (HIF-1α) and the malignant transformation of these cells. Mechanistic studies revealed that the increased expression of SESN2 is attributed to the demethylation of the SESN2 promoter induced by nickel, a process facilitated by decreased DNA methyl-transferase 3 A (DNMT3a) expression, while The downregulation of VHL transcription is linked to the suppression of the PP2A-C/GSK3β/β-Catenin/C-Myc pathway. Additionally, we discovered that SESN2-mediated autophagy triggers the degradation of HUR protein, which subsequently reduces the stability of USP28 mRNA and inhibits the PP2A-C/GSK3β/β-Catenin pathway and c-Myc transcription in HBECs post nickel exposure. Our results reveal that nickel exposure leads to the downregulation of DNMT3a, resulting in the hypomethylation of the SESN2 promoter and its protein induction. This triggers autophagy-dependent suppression of the HUR/USP28/PP2A/β-Catenin/c-Myc pathway, subsequently leading to reduced VHL transcription, accumulation of HIF-1α protein, and the malignant transformation of human bronchial epithelial cells (HBECs). Our research offers novel insights into the molecular mechanisms that underlie the lung carcinogenic effects of nickel exposure. Specifically, nickel induces aberrant DNA methylation in the SESN2 promoter region through the decrease of DNMT3a levels, which ultimately leads to HIF-1α protein accumulation and the malignant transformation of HBECs. Specifically, nickel initiates DNA-methylation of the SESN2 promoter region by decreasing DNMT3a, ultimately resulting in HIF-1α protein accumulation and malignant transformation of HBECs. This study highlights DNMT3a as a potential prognostic biomarker or therapeutic target to improve clinical outcomes in lung cancer patients. [Display omitted] • Nickel initiates aberrant DNA-methylation of the SESN2 promoter by reduction of DNMT3a levels. • SESN2-mediated autophagy resulted in degradation of the HUR protein following nickel exposure. • Autophagy-dependent attenuation of the HUR/USP28/PP2A/ß-Catenin/c-Myc axis to decrease in VHL transcription, accumulating HIF-1α protein and malignant transformation of human bronchial epithelial cells. [ABSTRACT FROM AUTHOR]

Geosmin is an environmental pollutant that causes off-flavor in water and aquatic products. The high occurrence of geosmin contamination in aquatic systems and aquaculture raises public awareness, however, few studies have investigated the response pathways of geosmin stress on freshwater fish. In this research, grass carp were exposed to 50 μg/L geosmin for 96 h, liver tissue was sequenced and validated using real-time qPCR. In total of 528 up-regulated genes and 488 down-regulated genes were observed, includes cytochrome P450 and uridine diphosphate (UDP)-glucuronosyltransferase related genes. KEGG analysis showed that chemical carcinogenesis-DNA adducts, metabolism of xenobiotics by cytochrome P450, drug metabolism-cytochrome P450 pathway was enriched. Common genes from the target genes of microRNAs and differential expression genes are enriched in metabolism of xenobiotics cytochrome P450 pathway. Two miRNAs (dre-miR-146a and miR-212–3p) down regulated their target genes (LOC127510138 and adh5 , respectively) which are enriched cytochrome P450 related pathway. The results present that geosmin is genetoxic to grass carp and indicate that cytochrome P450 system and UDP-glucuronosyltransferase play essential roles in biotransformation of geosmin. MicroRNAs regulate the biotransformation of geosmin by targeting specific genes, which contributes to the development of strategies to manage its negative impacts in both natural and artificial environments. [Display omitted] • Geosmin could induced mitochondrial damage in liver cell. • Geosmin present cytotoxic and genotoxic to grass carp. • CYP and UDP systems play important roles to cope with geosmin exposure. • dre-miR-146a and dre-miR-212–3p can be biomarker of geosmin exposure. [ABSTRACT FROM AUTHOR]

Centuries have passed without tobacco medical evaluation, and similar catastrophes have happened from the Roman Empire to now. We are not aware when, how and how much our body is exposed to chemical carcinogens every day. As a result of such exposure, millions of people fall ill with malignant diseases every year. The objectives of this work are: 1) Determination of the main urinary markers of exposure to the most dangerous chemical carcinogens; 2) Globally raising awareness about necessity of scientific testing chemicals before widespread human use; 3) Introducing the public about ubiquity of: As, Ni, Cr(VI), Cd, Be, and necessity of maximal reducing people′s exposure to them. There are well known causal relations between the most dangerous chemical carcinogens and different types of human malignant diseases. Population based studies may determine persons with high concentrations of the urinary markers/metabolites of the most dangerous chemical carcinogens. Then, such selected persons should be removed from such circumstances and/or regularly checked. Better solution is to find out the source(s) of incriminated chemical cancerogens and eliminate or mitigate their emission. These are a kind of (pre)screening (primordial prevention) for persons with high risk of developing malignant diseases causally related to the most dangerous chemical carcinogens. [ABSTRACT FROM AUTHOR]

Polycyclic aromatic hydrocarbons (PAHs), in particular benzo [ a ]pyrene (BaP), have been identified as carcinogenic components of tobacco smoke. In mammals, the toxicological response to BaP-diol-epoxide is driven by cytochrome P450 (CYP1A1), a pathway which is absent in Caenorhabditis elegans. In contrast, in worms prominently the CYP-35 enzyme family seems to be induced after BaP exposure. In C. elegans , BaP exposure reduces the accumulation of lysosomal neutral lipids in a dose dependent manner and the deletion of cyp-35A2 results in a significant elevation of neutral lipid metabolism. A cyp-35A2 :mCherry ;unc-47 :GFP dual-labelled reporter strain facilitated the identification of three potential upstream regulators that drive BaP metabolism in worms, namely elt-2, nhr-49 and fos-1. This newly described reporter line is a powerful resource for future large-scale RNAi regarding toxicology and lipid metabolism screens. [Display omitted] • BaP reduces the accumulation of lysosomal neutral lipids in C. elegans. • Deletion of cyp-35A2 results in a significant increase in neutral lipids. • Creation of a dual-labelled reporter strain cyp-35A2 :mCherry ;unc-47 :GFP. • Elt-2, nhr-49 and fos-1 are potential upstream regulators of BaP metabolism. • The reporter is a resource for toxicology and lipid metabolism screens. [ABSTRACT FROM AUTHOR]

We present a computational study on derivatives of the anticancer VCp 2 Cl 2 and their interaction with bases of DNA. The derivatives were obtained by substituting the cyclopentadiene of VCp 2 Cl 2 by ligands H 2 O , NH 3 , C 2 O 4 2 − , OH − , Cl − and O 2 −. Oxidation states IV and V of vanadium were considered, a total of 20 complexes are included. This study addresses the role of ligands in the interaction of vanadium complexes with nucleophilic sites of guanine, adenine, cytosine and thymine. The methodology M06-2X/cc-pVTZ was employed, and the effects of the solvent were considered. Results suggest that there is a high affinity for guanine and cytosine, particularly when H 2 O and NH 3 ligands are considered. These findings are confirmed by the bond lengths, bond orders and charge analysis. Our results provide a clue about the ligands that favor the interaction of vanadium with DNA bases and may help the future design of vanadium-based anticancer drugs. • There is a high affinity between vanadium and adenine and guanine. • Vanadium(IV) and (V) complexes bind preferentially to guanine and cytosine. • We give a clue about how vanadium compounds may interact with biological targets. • For V(IV) and V(C), water and amino ligands forms the most stable adduct with DNA bases. [Display omitted] [ABSTRACT FROM AUTHOR]

In this study, we identified AFB1 adducts as potential markers and investigated the role of curcumin in alleviating AFB1-induced liver damage by suppressing the production of AFB1 adducts and oxidative stress in AA broilers liver. A total of 64 one-day-old Arbor Acres (AA) broilers were randomly divided into four groups, including control group, AFB1 group (5 mg/kg AFB1), cur + AFB1 group (300 mg/kg curcumin+5 mg/kg AFB1) and curcumin group (300 mg/kg). Serum biochemical parameters, liver antioxidant abilities, AFB1 adducts and oxidative stress mechanism were studied in broilers. AFB1 administration accompany with signs of liver injury, including hepatic histological lesions, increased serum enzymes activities, decreased liver antioxidant enzymes activities and the suppression of ROS and 8-OHdG. Meanwhile, Nrf2/HO-1 pathway was depressed by AFB1 treatment. Immunohistochemistry and ELISA showed that AFB1 significantly increased AFB1-DNA adduct in liver (p < 0.05) and AFB1-lysine adduct in serum (p < 0.05). Importantly, supplementation of curcumin can ameliorate these alterations. Intriguingly, curcumin alleviated AFB1-induced toxicity and oxidative stress by inhibiting the generation of ROS, 8-OHdG and AFB1 adducts, and activated Nrf2 signaling pathway in broilers. Conclusively, our experiments suggest that curcumin could be considered as a potential agent for prevention of AFB1-induced toxicity and oxidative stress, and AFB1 adducts could be suitable therapeutic targets. Image 1 • Aflatoxin B1 adducts can be used as biomarkers for evaluation of exposure to Aflatoxin B1 induced liver damage. • Aflatoxin B1-DNA adduct and Aflatoxin B1-lysine adduct were first determined by IHC and ELISA in chicken. • Aflatoxin B1 may cause liver damage via Aflatoxin B1 adducts in chicken. • Curcumin ameliorates the Aflatoxin B1-induced liver damage via reduction of Aflatoxin B1 adducts. [ABSTRACT FROM AUTHOR]

DNA adducts are associated with a number of diseases, including cancer. Based on a recent report by our group, the aim of this study was to test the hypothesis that DNA adducts can be removed by means of one or more of the following three intervention programmes: intermittent whole-body hyperthermia; detoxification; and cell repair. The number of DNA adducts and total DNA adduct concentrations were measured in 104 patients who underwent one or more of the three intervention programmes. DNA adduct assessments were carried out on extracted genomic DNA by gas-liquid chromatography, with any DNA adducts found being localised using DNA microarrays. The baseline median number of DNA adducts was 2. The follow-up median number of adducts was highly significantly lower at 0 (p < 0.000000000000003). The mean total DNA adduct concentration at baseline was 9.308 ng/mL, and highly significantly lower at follow-up at 1.553 ng/mL (p < 0.000000000000006). Of the three intervention programmes, only the intermittent whole-body hyperthermia was associated with a significant reduction in DNA adducts. This study offers support for the hypothesis that DNA adducts can be removed by intermittent whole-body hyperthermia. The intermittent hyperthermia used involved infrared-A (wavelength 700-1400 nm, or, equivalently, a frequency of 215-430 THz) being preferentially delivered to the whole body, apart from the head, for up to one hour per session, with gradual core body temperature elevation usually occurring during the first 20-30 min. These results may offer an explanation at the molecular level for other reported clinical benefits of intermittent whole-body hyperthermia. [ABSTRACT FROM AUTHOR]

The toxicity of acrylamide (AA) has continuously attracted wide concerns as its extensive presence from both environmental and dietary sources. However, its hepatic metabolic transformation and metabolic fate still remain unclear. This study aims to unravel the metabolic profile and glutathione (GSH) mediated metabolic fate of AA in liver of rats under the dose-dependent exposure. We found that exposure to AA dose-dependently alters the binding of AA and GSH and the generation of mercapturic acid adducts, while liver as a target tissue bears the metabolic transformation of AA via regulating GSH synthesis and consumption pathways, in which glutamine synthase (GSS), cytochrome P450 2E1 (CYP2E1), and glutathione S-transferase P1 (GSTP1) play a key role. In response to high- and low-dose exposures to AA, there were significant differences in liver of rats, including the changes in GSH and cysteine (CYS) activities and the conversion ratio of AA to glycidamide (GA), and liver can affect the transformation of AA by regulating the GSH-mediated metabolic pathway. Low-dose exposure to AA activates GSH synthesis pathway in liver and upregulates GSS activity and CYS content with no change in γ-glutamyl transpeptidase 1 (GGT1) activity. High-dose exposure to AA activates the detoxification pathway of GSH and increases GSH consumption by upregulating GSTP1 activity. In addition, molecular docking results showed that most of the metabolic molecules transformed by AA and GA other than themselves can closely bind to GSTP1, GSS, GGT1, N-acetyltransferase 8, and dimethyl sulfide dehydrogenase 1. The binding of AA-GSH and GA-GSH to GSTP1 and CYP2E1 enzymes determine the tendentiousness between toxicity and detoxification of AA, which exerts a prospective avenue for targeting protective role of hepatic enzymes against in vivo toxicity of AA. [Display omitted] • Conversion of acrylamide (AA) into glycidamide corresponds to binding of AA with GSH. • Liver bears transformation of AA via regulating GSH synthesis and consumption pathways. • Exposure to AA at 10 mg/kg activates GSH synthesis pathway and upregulates GSS activity. • Exposure to AA at 50 mg/kg activates GSH detoxification pathway and upregulates GSTP1 activity. • Binding of AA-GSH and GA-GSH with GSTP1 and CYP2E1 determine the tendentiousness. [ABSTRACT FROM AUTHOR]

Benzo [a]pyrene (B [a]P) is a widespread environmental chemical pollutant that has been linked to the development of various diseases. However, the specific mechanism of action remains unclear. In this study, human bronchial epithelial 16HBE and BEAS-2B cells were exposed to B [a]P at 0–32 μM to assess the DNA-damaging effects. B [a]P exposure resulted in elevated expression of γ-H2AX, a marker of DNA damage. The m6A RNA methylation assay showed that B [a]P exposure increased the extent of m6A modification and the demethylase ALKBH5 played an integral role in this process. Moreover, the results of the comet assay and Western blot analysis showed an increase in m6A modification mediated by ALKBH5 that promoted DNA damage. Furthermore, the participation of a novel circular RNA, circ_0003552, was assessed by high-throughput sequencing under the condition of high m6A modification induced by B [a]P exposure. In subsequent functional studies, an interference/overexpression system was created to confirm that circ_0003552 participated in regulation of DNA damage. Mechanistically, circ_0003552 had an m6A binding site that could regulate its generation. This study is the first to report that B [a]P upregulated circ_0003552 through m6A modification, thereby promoting DNA damage. These findings revealed that epigenetics played a key role in environmental carcinogen-induced DNA damage, and the quantitative changes it brought might provide an early biomarker for future medical studies of genetic-related diseases and a new platform for investigations of the interaction between epigenetics and genetics. [Display omitted] • B [a]P induces DNA damage in bronchial epithelial cells. • B [a]P upregulates the degree of m6A modification by suppressing ALKBH5 expression. • Both ALKBH5 and circ_0003552 can regulate the B [a]P-induced DNA damage. • M6A modification promotes circ_0003552 production through the m6A binding site. [ABSTRACT FROM AUTHOR]

Aromatic amines (AAs) are polar organic chemicals with a wide environmental distribution originating from various sources, such as tobacco smoke, diesel exhaust, and dermal absorption from textile products with azo dyes. The toxicity profile of AAs is directly related to the amino group's metabolic activation and the generation of the reactive intermediate, forming DNA adducts and potential carcinogenicity. Urinary levels of 8-hydroxy-2′-deoxyguanosine (8OHdG) are an important biomarker of DNA damage. Since AAs have been shown to cross the placental barrier, being a risk factor for adverse birth outcomes, prenatal exposure is a great public health concern. The present study aimed to measure the urinary levels of 58 AAs in Brazilian pregnant women (n = 300) and investigated the impact of this exposure on DNA damage by quantifying 8OHdG levels. The influence of tobacco smoke exposure and dermal absorption of AAs by clothes on urinary levels was also assessed. The results showed a 100% detection rate for eight AAs, two of them regulated by the European Union (2,6-dimethylaniline and 2,4-diaminotolune). Hundreds of AAs may be derived from aniline, which here showed a median of 1.38 ng/mL. Aniline also correlated positively with 2,6-dimethylaniline, p -aminophenol, and other AAs, suggesting exposure to multiple sources. The present findings suggest that both tobacco smoke and dermal contact with clothes containing azo dyes are potential sources that might strongly influence urinary levels of AAs in Brazilian pregnant women. A multiple regression linear model (R2 = 0.772) suggested that some regulated AAs (i.e., 2-naphthylamine and 4-aminobiphenyl), nicotine, smoke habit, age, and Brazilian region could induce DNA damage occurrence, increasing the levels of 8OHdG. Given the limited available data on human exposure to carcinogenic AAs, as well as the lack of toxicological information on those non-regulated, further studies focused on measuring their levels in human fluids and the potential exposure sources are clearly essential. [Display omitted] • Results showed a detection rate of 100% for eight aromatic amines (two regulated). • Aniline correlates with other aromatic amines, suggesting exposure to multiple sources. • Tobacco smoke and dermal contact with clothes are potential sources of aromatic amines. • Regulated aromatic amines and nicotine can induce DNA damage occurrence. [ABSTRACT FROM AUTHOR]

The work aimed to investigate the biocompatibility and biological activity of the water-soluble fullerene adduct C 60 -Arg. It was found that the material is haemocompatible, is not cyto- and genotoxic, possesses pronounced antioxidant activity. Additionally, this paper outlines the direction of application of water-soluble fullerene adducts in the creation of neuroprotectors. It has been suggested that a putative mechanism of the protective action of the C 60 -Arg adduct is associated with its antioxidant properties, the ability to penetrate the blood-brain barrier, and release nitrogen monoxide as a result of the catabolism of L-arginine residues, which promote vascular relaxation. The action of the C 60 -Arg adduct was compared with the action of such an antioxidant as Edaravone, which is approved in Japan for the treatment of ischemic and haemorrhagic strokes. In this article, we performed synthesis and identification of C 60 fullerene adduct with L-arginine (C 60 -Arg). As a result of study of complex investigation of biocompatibility and bioactivity it was shown that the adduct has a protective effect shown in in vivo experiments in the model of acute focal cerebral ischemia. Moreover, using molecular dynamics, structural and dynamic characteristics of C 60 -Arg in water were obtained. [Display omitted] [ABSTRACT FROM AUTHOR]

Exposure to arsenic, a widespread environmental toxin, produces multiple organ toxicity, including gastrointestinal toxicity. Nigella sativa (NS) has long been revered for its numerous health benefits under normal and pathological states. In view of this, the present study attempts to evaluate the protective efficacy of orally administered Nigella sativa oil (NSO) against arsenic-induced cytotoxic and genotoxic alterations in rat intestine and elucidate the underlying mechanism of its action. Rats were categorized into the control, NaAs, NSO, and NaAs+NSO groups. After pre-treatment of rats in the NaAs+NSO and NSO groups daily with NSO (2 ml/kg bwt, orally) for 14 days, NSO treatment was further continued for 30 days, with and without NaAs treatment (5 mg/kg bwt, orally), respectively. Various biochemical parameters, such as enzymatic and non-enzymatic antioxidants, carbohydrate metabolic and brush border membrane marker enzyme activities were evaluated in the mucosal homogenates of all the groups. Intestinal brush border membrane vesicles (BBMV) were isolated, and the activities of membrane marker enzyme viz. ALP, GGTase, LAP, and sucrase were determined. Further, the effect on kinetic parameters viz K M (Michaelis-Menten constant) and V max of these enzymes was assessed. Integrity of enterocyte DNA was examined using the comet assay. Histopathology of the intestines was performed to evaluate the histoarchitectural alterations induced by chronic arsenic exposure and/or NSO supplementation. Arsenic accumulation in the intestine was studied by inductively coupled plasma-mass spectroscopy (ICP-MS). NaAs treatment caused substantial changes in the activities of brush border membrane (BBM), carbohydrate metabolism, and antioxidant defense enzymes in the intestinal mucosal homogenates. The isolated BBM vesicles (BBMV) also showed marked suppression in the marker enzyme activities. Severe DNA damage and mucosal arsenic accumulation were observed in rats treated with NaAs alone. In contrast, oral NSO supplementation significantly alleviated all the adverse alterations induced by NaAs treatment. Histopathological examination supported the biochemical findings. NSO, by improving the antioxidant status and energy metabolism, could significantly alter the ability of the intestine to protect against free radical-mediated arsenic toxicity in intestine. Thus, NSO may have an excellent scope in managing gastrointestinal distress in arsenic intoxication. [ABSTRACT FROM AUTHOR]

To prevent the non-acceptable effects of agrochemicals on arable fields, Environmental Risk Assessment (ERA) aims to assess and protect against a wide range of risks due to stressors to non-target species. While exposure to stress is a key factor in ERA models, exposure values are difficult to obtain and rely on laboratory studies with often debatable relevance to field situations. To improve intake estimates, data from realistic field-based scenarios are needed. We developed calibration curves relating known seed numbers of up to 20 onion and carrot seeds consumed by wild-caught wood mice (Apodemus sylvaticus) to the seed DNA content in the feces. Based on these inferred quantitative relationships, a field trial was run to determine seed intake in a natural setting using realistic levels of seed spillage. Onion DNA was detected in the fecal samples of the wood mice caught in the field, which resembled a seed intake of up to 1 onion seed. No intake of carrot seeds was detected. This is the first-ever study to quantify seed intake in a realistic field scenario using a DNA-based analysis, showing that accurate seed intake estimates can be obtained. Our approach can help to improve risk assessment models through its minimally-invasive and accurate assessment of seed intake by ERA representative and non-target species, which would otherwise be undetectable with traditional methods. Our novel approach and its results are highly relevant to studies of food intake and diet composition for basic and applied research alike. • Seed intake is difficult to estimate for risk assessments of small mammals. • Seed intake estimates of wood mice were obtained via DNA-based analysis in the lab. • We obtained calibration curves (R2 >0.57) relating seed intake vs. fecal DNA content. • In a realistic field scenario, we quantified seed intake of wild-caught wood mice. • Accurate assessment of seed intake using a DNA-based analysis can enhance ERA. [ABSTRACT FROM AUTHOR]

A taxonomic study was conducted on 16 bacterial strains isolated from wild Adélie penguins (Pygoscelis adeliae) from Seymour (Marambio) Island and James Ross Island. An initial screening by repetitive sequence-based PCR fingerprinting divided the strains studied into four coherent groups. Phylogenetic analysis based on 16S rRNA gene sequences assigned all groups to the genus Corynebacterium and showed that Corynebacterium glyciniphilum and Corynebacterium terpenotabidum were the closest species with 16S rRNA gene sequence similarities between 95.4 % and 96.5 %. Further examination of the strains studied with ribotyping, MALDI-TOF mass spectrometry, comprehensive biotyping and calculation of average nucleotide identity and digital DNA–DNA hybridisation values confirmed the separation of the four groups from each other and from the other Corynebacterium species. Chemotaxonomically, the four strains P5828T, P5850T, P6136T, P7210T representing the studied groups were characterised by C 16:0 and C 18:1 ω9c as the major fatty acids, by the presence of meso -diaminopimelic acid in the peptidoglycan, the presence of corynemycolic acids and a quinone system with the predominant menaquinone MK-9(H 2). The results of this study show that the strains studied represent four new species of the genus Corynebacterium , for which the names Corynebacterium antarcticum sp. nov. (type strain P5850T = CCM 8835T = LMG 30620T), Corynebacterium marambiense sp. nov. (type strain P5828T = CCM 8864T = LMG 31626T), Corynebacterium meridianum sp. nov. (type strain P6136T = CCM 8863T = LMG 31628T) and Corynebacterium pygosceleis sp. nov. (type strain P7210T = CCM 8836T = LMG 30621T) are proposed. [ABSTRACT FROM AUTHOR]

PM 2.5 exposure leads to lung function alteration. The potential pathway underlying above association, especially the role of DNA methylation is unclear. The objectives of this study are to evaluate the associations of personal PM 2.5 concentrations with DNA methylation at the epigenome-wide level, and investigate how PM 2.5 -related DNA methylation affects lung function. A total of 402 observations of non-smokers were selected from the Wuhan-Zhuhai cohort. PM 2.5 exposure was estimated through a model established in the same population. Blood DNA methylation levels were determined through Illumina Infinium MethylationEPIC BeadChips. Lung function was tested through spirometry on the day of blood sampling. The associations of PM 2.5 exposure with DNA methylation and DNA methylation with lung function were determined through linear mixed models. Ten PM 2.5 -related CpG sites (mapped to 7 different genes) were observed with false discovery rate <0.05. Methylation levels of cg24821877, cg24862131, cg23530876, cg11149743 and cg10781276 were positively associated with PM 2.5 concentrations. While methylation levels of cg10314909, cg08968107, cg18362281, cg24663971 and cg17834632 were negatively associated with PM 2.5 concentrations. The top CpG was cg24663971 (P = 1.51✕10−9). Among the above 10 sites, significantly positive associations of methylation levels of cg24663971 with FVC%pred and FEV 1 %pred, and cg10314909 with FVC, FVC%pred, and FEV 1 %pred were observed. Age had modification effect on the associations between cg24663971 methylation and FVC%pred, and the associations were more obvious among participants with age ≥58 years. In conclusion, PM 2.5 exposure was associated with DNA methylation, and PM 2.5 -related DNA methylation was associated with lung function among Wuhan urban non-smokers. [Display omitted] • Ten CpGs were linked to PM 2.5 exposure with false discovery rate <0.05. • Cg24663971 and cg10314909 methylation was positively associated with lung function. • PM 2.5 exposure concentrations at the individual level were estimated. • Blood DNA methylation at the epigenome level were determined. [ABSTRACT FROM AUTHOR]

Studies have shown that lead (Pb) exposure caused genotoxicity, however, the underlying mechanisms remain unclear. A mechanism may be via DNA methylation which is one of the most widely studied epigenetic regulations for cellular activities. Whether this is involved in Pb-induced genotoxicity has rarely been studied. Our study aimed to examine whether DNA methylation was associated with Pb exposure and genotoxicity, and to explore its potential mediating roles. A total of 250 Pb-exposed workers were enrolled. Blood lead levels (BLLs) and genotoxic biomarkers (Micronuclei and Comet) were analyzed. Methylation levels at CpG sites of LINE1 and Alu and promoter region of P53 , BRCA1 , TRIM36 and OGG1 were measured by pyrosequencing. Generalized linear model (GLM) combined with restricted cubic splines (RCS) were used to analyze relationships between Pb exposure, DNA methylation and genotoxicity. Mediation effect was used to explore mediating roles of DNA methylation. The distribution of BLLs was right-skewed and showed wide ranges from 23.7 to 636.2 μg/L with median (P 25 , P 75) being 218.4 (106.1, 313.9) μg/L among all workers. Micronuclei frequencies showed Poisson distribution [1.94 ± 1.88‰] and Comet tail intensity showed normal distribution [1.69 ± 0.93%]. GLM combined with RCS showed that Alu methylation was negatively associated with BLLs, while P53 and OGG1 methylation were positively associated with BLLs. Micronuclei were negatively associated with Alu and TRIM36 methylation but positively with P53 methylation. Comet was positively associated with P53 and BRCA1 methylation. Mediation effect showed that Alu methylation mediated 7% effects on association between Pb exposure and micronuclei, whereas, P53 methylation mediated 14% and BRCA1 mediated 9% effects on association between Pb exposure and Comet. Our data show that Pb exposure induced changes of global and gene-specific DNA methylation which mediated Pb-induced genotoxicity. [Display omitted] • Alu methylation was negatively associated with BLLs among Pb-exposed workers. • Micronuclei frequencies were negatively associated with Alu methylation. • Alu methylation mediated 7% effects on association between BLLs and micronuclei. • Comet tail intensities were positively associated with P53 and BRCA1 methylation. • P53 and BRCA1 methylation mediated association between BLLs and Comet. [ABSTRACT FROM AUTHOR]

Fine particle (PM 2.5 , less than 2.5 micrometers in diameter) is regarded as a harmful carcinogen. However, the molecular mechanisms of the carcinogenic effects of ambient fine particles have not been fully elucidated, and therapeutic options to address this major public health challenge are lacking. Here, we present global gene-specific DNA methylation and transcriptomic (RNA-Seq) analyses after HBE cells were exposed to fine particles on a portable, small, and all-in-one organ-level lung-mimicking air-liquid interface exposure (MALIE) microfluidic platform. A series of cancer-related signal transduction pathways were activated. ErbB1, ErbB2, and ErbB3 gene expression altered by fine particle exposure was the result of changes in the cellular DNA methylome. The protein expression of ErbB family was inhibited by drugs and could regulate downstream Grb2/Raf pathway and Akt/MDM2 pathway. All of the above results indicated that ErbB family may be promising drug targets for air pollution-related diseases and that inhibitor drugs can be used as therapeutic options to treat these diseases. [Display omitted] • A microfluidic system that mimics lung functions for cells exposure. • ErbB family gene expression altered by PM2.5 due to the DNA methylome. • The inhibited-phosphorylated ErbB family could regulate pathways. • Downstream AKT/MDM2 pathway and Grb2/RAF pathway were activated. [ABSTRACT FROM AUTHOR]

Lipid peroxidation products react with cellular molecules, such as DNA bases, to form covalent adducts, which are associated with aging and disease processes. Since lipid peroxidation is a complex process and occurs in multiple stages, there might be yet unknown reaction pathways. Here, we analyzed comprehensively 2?-deoxyguanosine (dG) adducts with oxidized arachidonic acid using liquid chromatography–tandem mass spectrometry and found the formation of 7-(2-oxo-hexyl)-etheno-dG as one of the major unidentified adducts. The formation of this adduct was reproduced in the reaction of dG with 2-octenal and predominantly with 4-oxo-2-octenal (OOE). We also found that other 2-alkenals (with five or more carbons) generate corresponding 4-oxo-2-alkenal-type adducts. Importantly, it was found that transition metals enhanced the oxidation of C4-position of 2-octenal, leading to the formation of OOE-dG adduct. These findings demonstrated a new pathway for the formation of 4-oxo-2-alkenals during lipid peroxidation and might provide a mechanism for metal-catalyzed genotoxicity. 4-Oxo-2-alkenals, which are highly reactive to nucleosides, are generated through metal-catalyzed oxidation of corresponding 2-alkenals during lipid peroxidation. [ABSTRACT FROM PUBLISHER]

Résumé La néphropathie aux acides aristolochiques (NAA) est une néphropathie toxique caractérisée par une fibrose rénale interstitielle progressive et fréquemment associée à un cancer des voies urinaires. Elle a été rapportée initialement en Belgique suite à l’ingestion de préparations à visée amaigrissante contenant une plante chinoise, l’ Aristolochia fangchi . Depuis lors, de nombreux cas sont rapportés dans le monde, en particulier en Asie. Des modèles expérimentaux de néphropathie aux acides aristolochiques (AA) ont été mis au point. Ils confirment la relation de cause à effet entre l’administration d’AA et le développement d’une toxicité rénale aiguë et chronique, compliquée de cancers des voies urinaires. L’établissement de ces modèles expérimentaux représente une réelle opportunité pour l’étude des mécanismes de la fibrose rénale interstitielle et la cancérogenèse. En termes de santé publique, l’histoire de cette néphropathie montre qu’il est nécessaire de soumettre les « médecines naturelles » aux même contrôles d’efficacité, de toxicité et de conformité que les médicaments de la chaîne pharmaceutique. Devant toute observation inhabituelle d’insuffisance rénale et/ou de cancer des voies urinaires, il est indispensable d’évoquer l’exposition aux AA. La confirmation par analyse phytochimique de l’ingestion de produits contenant des AA n’est pas toujours réalisable. Néanmoins, la ponction biopsie rénale demeure un élément clé du diagnostic par la démonstration d’une fibrose interstitielle hypocellulaire d’intensité décroissante selon un gradient corticomédullaire, surtout au stade avancé de la néphropathie. En outre, la détection d’adduits d’ADN spécifiques aux AA dans un échantillon tissulaire rénal ou urétéral permet de confirmer une exposition antérieure aux AA. La persistance de ces adduits d’ADN dans les tissus cibles se chiffre en années. Enfin, un dépistage urologique s’impose au vu du potentiel carcinogène des AA. Aristolochic acid nephropathy is a renal disease of toxic origin characterized by a progressive interstitial fibrosis and frequently associated with urinary tract cancer. It was initially reported in Belgium after the intake of slimming pills containing root extracts of a Chinese herb, Aristolochia fangchi . In the following decades, numerous cases have been reported worldwide, particularly in Asian countries. Several experimental models of aristolochic acid nephropathy (AAN) have been designed. They confirm the causal link between AA exposure and the onset of acute and chronic renal toxicity, as well as urinary tract cancer. These experimental models offer the opportunity to study the mechanisms of renal interstitial fibrosis and carcinogenesis. In terms of public health, the history of this nephropathy demonstrates that it is mandatory to submit all “natural medicinal products” to the same controls of efficacy, toxicity and conformity applied to the classical drugs derived from the pharmaceutical producers. Any unusual observation of renal failure and/or cancer of the urinary tract should lead to a questioning about any prior exposure to AA. The confirmation of the ingestion of AA containing compounds by phytochemical analysis is not always feasible. However, the renal biopsy remains a crucial diagnostic point through the demonstration of a hypocellular interstitial fibrosis with a decreasing corticomedullary gradient, mostly in advanced cases of kidney disease. Moreover, the detection of AA-related DNA adducts within a renal or urothelial tissue sample could confirm the prior AA exposure. The persistence of these specific DNA adducts in renal tissue is very long (up to 20 years). Finally, considering the highly carcinogenic properties of AA, a systematic endo-urological screening is absolutely necessary. [ABSTRACT FROM AUTHOR]

This study quantified the temporal variability of concentration of carcinogenic polycyclic aromatic hydrocarbons (c-PAHs), genotoxicity, oxidative DNA damage and dioxin-like activity of the extractable organic matter (EOM) of atmospheric aerosol particles of aerodynamic diameter (d ae, μm) coarse (1 < d ae < 10), upper- (0.5 < d ae < 1) and lower-accumulation (0.17 < d ae < 0.5) and ultrafine (<0.17) fractions. The upper accumulation fraction formed most of the aerosol mass for 22 of the 26 study days and contained ∼44% of total c-PAHs, while the ultrafine fraction contained only ∼11%. DNA adduct levels suggested a crucial contribution of c-PAHs bound to the upper accumulation fraction. The dioxin-like activity was also driven primarily by c-PAH concentrations. In contrast, oxidative DNA damage was not related to c-PAHs, as a negative correlation with c-PAHs was observed. These results suggest that genotoxicity and dioxin-like activity are the major toxic effects of organic compounds bound to size segregated aerosol, while oxidative DNA damage is not induced by EOM. [ABSTRACT FROM AUTHOR]

The aim of the present study was to confirm the relevance of studying DNA adduct formation in a field study. In that context, freshwater mussels Dreissena polymorpha , collected in a reference station, were transplanted in different sites with a pollution gradient. After one and two months, mussels were collected and DNA adduct formation was analyzed using the 32 P post labelling technique on both gills and digestive glands. In addition, the expression of genes involved in the detoxification system (catalase (CAT), superoxide dismutase (SOD), glutathione S-transferase (GST), HSP70, aryl hydrocarbon receptor (AHR), P glycoprotein (PgP), metallothionein (MT)) was assessed by RT-PCR. DNA adducts were observed at amount comparable to data from literature. Increase of DNA adducts after two months of transplantation could be correlated with strong modulation of gene expression implicated in detoxification processes. Indeed, PgP and HSP70 gene expressions were similarly induced in gills and digestive glands while SOD and CAT expressions were down regulated in both tissues. AHR, GST and MT genes were differently regulated depending upon the tissue studied and the level of contamination in the different sites. We demonstrated that mussels transplanted in the different stations with pollution gradient were able to biotransform PAHs, assessed by DNA adduct formation and the high decrease of detoxification genes. Specific DNA adducts pattern obtained after one and two month mussel transplantations demonstrated the relevance of DNA adduct as biomarker of environmental pollution. [ABSTRACT FROM AUTHOR]

Copyright of Collegium Antropologicum is the property of Croatian Anthropological Society and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

In Tongliang, China, a coal-fired power plant was the major pollution source until its shutdown in 2004. We enrolled two cohorts of nonsmoking women and their newborns before and after the shutdown to examine the relationship between prenatal exposure to polycyclic aromatic hydrocarbons (PAHs) and fetal and child growth and development. PAHs were used to measure exposure to air pollution generated by the power plant. Using PAH–DNA adduct levels as biomarkers for the biologically effective dose of PAH exposure, we examined whether PAH–DNA adduct levels were associated with birth outcome, growth rate, and neurodevelopment. Head circumference was greater in children of the second cohort, compared with the first (p = 0.001), consistent with significantly reduced levels of cord blood PAH–DNA adducts in cohort II (p < 0.001) and reduced levels of ambient PAHs (p = 0.01). [Copyright &y& Elsevier]

Despite the adverse effects of smoking, many pregnancies are exposed to tobacco smoke. Recent studies have investigatedwhether smoking damages placentalDNA by measuring DNA adducts. This study investigated whether a more severe lesion, double-strand DNA breaks, was also present in the tobacco smoking-exposed placenta. Term placentae from women who smoked during their entire pregnancies (n = 52), fromthosewho had ceased smoking for at least 4 weeks before delivery (previous smokers, n = 34), and from nonsmoking women (n = 150) were examined using the DNA double-strand break marker phosphorylated γ H2AX. The extent of DNA damage was assessed according to cell type and additional markers were applied for cell fate (apoptosis and DNA repair), and function (human chorionic gonadotropin, human placental lactogen, and glucose transporter 1), to characterize the effect of the DNA damage on placental integrity. Marked phosphorylated γ H2AX-positive cells occurred in the villous syncytiotrophoblast and syncytial knot nuclei in placentae from smokers (P b .001). Phosphorylated γ H2AX foci did not colocalize with the DNA repair protein 53BP1, and damaged nuclei had a marked reduction in expression of human chorionic gonadotropin, human placental lactogen, and glucose transporter 1. Minimal DNA damage, similar to nonsmokers, was present in previous smokers including those that had ceased smoking for just over 4 weeks before delivery. In summary, smoking during pregnancy was associated with marked doublestrand DNA break damage to the syncytiotrophoblast. We suggest that smoking cessation is important to prevent additional DNA damage and to facilitate DNA repair. [ABSTRACT FROM AUTHOR]

The article focuses on a study that was conducted to examine the enhancing effect of a cysteinyl thiol on the antioxidant activity of Myricetin, a naturally occurring flavonoid. It mentions the procedure where High-performance liquid chromatography (HPLC) analysis was performed on Myricetin in the presence of the thiol. It reveals that two thiol adducts discovered on the B ring of myricetin indicates its enhancing effect on the antioxidant activity of Myricetin.

Abstract: Mitomycin C is a DNA alkylating agent activated by bioreduction. It has been in clinical use against a range of solid tumours since the 1960s. Its DNA adduct formation mechanism has been extensively studied and it therefore presents an excellent test case for the applicability of Density Functional Theory (DFT) calculations based on simple model systems. The reaction cascades proposed in the literature were calculated and the results revealed that many of the mechanistic features were correctly predicted: the one- and two-electron reduction was deemed plausible, the pH-dependence of the rate of aziridine ring opening, and that the alkylating agent is required to be formed in the proximity of DNA for adduct formation to occur. The DFT method was unable to predict where adduct formation takes place on the guanine based on the exothermicity of the nucleophilic attack. Overall, the DFT method does well to predict the mechanism for adduct formation considering that the model systems are simple and modest CPU requirements. [Copyright &y& Elsevier]

Regular exercise has recognized health benefits, partly because it reportedly lowers the levels of the oxidation products of proteins and DNA at rest, in contrast with the effect of acute exercise. However, when we compared oxidative response markers in active middle-aged subjects with those in sedentary ones, the level of urinary 8-OHdG was higher in active subjects. Because neutrophils are the first line of defense against a variety of infectious diseases, we then compared the cell density, functions and apoptosis of neutrophils in active subjects with those in sedentary ones. The cell density of neutrophils and phagocytosis of opsonized zymosan by neutrophils were higher in active subjects, being similar with the reported effects of acute exercise. To determine any beneficial effects of oxidative stress in active subjects, we then compared the levels of antibodies against 4- hydroxy-2-nonenal adducts in active subjects with those in sedentary ones, because 4-hydroxy-2-nonenal is one of the most common bioactive aldehyde products of oxidative stress, and because the IgM class of antibodies against oxidized low-density lipoprotein is associated with atheroprotective properties. The level of the IgM but not the IgG class of antibodies against 4-hydroxy-2-nonenal adducts was higher in active subjects. Overall, this study revealed that our active middle-aged subjects showed both oxidative responses and a higher IgM response to reactive carbonyl derivatives, possibly providing a basis for a health benefit by exercise in our active subjects [ABSTRACT FROM AUTHOR]

Background. Ellipticine and doxorubicin are antineoplastic agents, whose action is based mainly on DNA damage such as intercalation, inhibition of topoisomerase II and formation of covalent DNA adducts. The key target to resolve which of these mechanisms are responsible for ellipticine and doxorubicin anticancer effects is the development of suitable methods for identifying their individual DNA-damaging effects. Here, the 32P-postlabeling method was tested to detect covalent DNA adducts formed by ellipticine and doxorubicin. Methods. The standard procedure of 32P-postlabeling assay, this procedure under ATP-deficient conditions, the version using extraction of adducts with n-butanol and the nuclease P1 enrichment version were used to analyze ellipticineand/ or doxorubicin-derived DNA adducts. Results. Two covalent ellipticine-derived DNA adducts, which are associated with cytotoxicity of ellipticine to human UKF-NB-3 and UKF-NB-4 neuroblastoma cell lines, were detected by the 32P-postlabeling method. These adducts are identical to those formed by the ellipticine metabolites, 13-hydroxy- and 12-hydroxyellipticine. In contrast, no covalent adducts formed by doxorubicin in DNA of these neuroblastoma cells and in DNA incubated with this drug and formaldehyde in vitro were detectable by the 32P-postlabeling assay. Conclusions. The results presented in this paper are the first to demonstrate that in contrast to covalent DNA adducts formed by ellipticine, the adducts generated by formaldehyde-mediated covalent binding of doxorubicin to DNA are not detectable by the 32P-postlabeling assay. No DNA adducts were, detectable either in vitro, in incubations of DNA with doxorubicin or in DNA of neuroblastoma cells treated with this drug. The results also suggest that covalent binding of ellipticine to DNA of UKF-NB-3 and UKF-NB-4 neuroblastoma cell lines is the predominant mechanism responsible for the cytotoxicity of this drug. To understand the mechanisms of doxorubicin anticancer effects on neuroblastoma cells, development of novel methods for identifying covalent doxorubicin-derived DNA adducts is the major challenge for further research. [ABSTRACT FROM AUTHOR]

Abstract: Biological markers of produced water (PW) exposure were studied in Atlantic cod (Gadus morhua) in both laboratory and field experiments, using authentic PW from a North Sea oil field. In the laboratory study, the PW exposure yielded significantly elevated levels of metabolites of polycyclic aromatic hydrocarbons (PAHs) and alkylphenols (APs) in bile even at the lowest exposure dose (0.125% PW). Other biomarkers (hepatic CYP1A induction and DNA adduct formation) responded at 0.25% and 0.5% PW concentrations. In the field study, bile metabolite markers and hepatic CYP1A were clearly increased in fish caged close to the PW outfall. Induction of plasma vitellogenin was not found in laboratory or field exposures, suggesting that the levels of oestrogen agonists (such as APs) might not have been sufficient to elicit induction, under the present conditions. The applicability of the biomarkers for use in water column biomonitoring programs is discussed. [Copyright &y& Elsevier]

Abstract: Contaminated sediments may have wide-ranging impacts on human and ecological health. A series of in situ caged exposure studies using juvenile Chinook salmon was conducted in the Lower Duwamish Waterway (LDW). Chemical analysis of sediment, water, and fish tissue were completed. Additionally, in 2004, DNA adducts in hepatic and gill tissues were measured. Gills contained significantly higher DNA adducts at stations B2 and B4, prompting further analysis of gills in 2006 and 2007. Fluorescent aromatic compounds (FACs) in bile, and CYP1A1 in hepatic tissue were also measured during 2006 and 2007, respectively. FACs in field-caged fish were comparable or significantly higher than wild-caught fish LDW fish and significantly higher than lab fish after only 8–10days, demonstrating the equivalency of exposure to that of migrating salmon. Furthermore, selected biomarkers appear to be capable of detecting spikes in contamination between sampling years, emphasizing the need for multiple year data collection. [Copyright &y& Elsevier]

Abstract: Why does O6-methylguanine-DNA methyltransferase (MGMT), an indispensable DNA repair enzyme, have a mechanism which seems to run counter to its importance? This enzyme is key to the removal of detrimental alkyl adducts from guanine bases. Although the mechanism is well known, an unusual feature surrounds its mode of action, which is its so-called suicidal endpoint. In addition, induction of MGMT is highly variable and its kinetics is atypical. These features raise some questions on the seemingly paradoxical mechanism. In this manuscript we point out that, although there is ample literature regarding the “how” of the MGMT enzyme, we found a lack of information on “why” this specific mechanism is in place. We then ask whether we know all there is to know about MGMT, or if perhaps there is a further as yet unknown function for MGMT, or if the suicidal mechanism may play some kind of protective role in the cell. [Copyright &y& Elsevier]

Abstract: Theoretical insight into the formation mechanism of C8 adducts in a series of complicated carcinogenic reactions has been provided in some previous works. However, the actual C8 deprotonation process involved in this mechanism requires further detailed elucidation. In this paper, we first present the structural features of a proton wire related to the C8 deprotonation process in terms of ABEEM/MM-MD simulations. Then, on the basis of MD simulations, appropriate theoretical models are constructed to study the C8 deprotonation process, and the energetics of the deprotonation process are determined by employing ab initio and DFT methods. The obtained results agree with experimental observations. This study supports the mechanism of formation of C8 adducts in actual carcinogenic reactions, where arylnitrenium ions directly attack at the C8 positions of nucleoside bases in DNA. [ABSTRACT FROM AUTHOR]

Abstract: Exposure to chemicals like benzo(a)pyrene (BaP) can lead to structural changes in DNA and as a consequence to increased incidence of diseases with a genetic basis, as well as oxidative stress in the testis. However its ability to induce oxidative DNA damage in germ cells is not fully investigated. In the present study, BaP was used to induce 8-hydroxydeoxyguanosine (8-OHdG), a specific DNA adducts for oxidative DNA damage, in testis and epididymal sperm and the possible protection role of radish and/or cress was investigated. The results revealed that BaP induced a significant increase in DNA damage in both tissues, as indicated by increased DNA strand breaks in a fluorimetric analysis of DNA unwinding (FADU). Furthermore, it increased the oxidative damage in epididymal sperm, as indicated by the increase in sperm abnormalities, lipid peroxidation (LPO), accompanied with a decrease in glutathione content (GSH), sperm count and sperm motility as well as induction of filtration in the histology of the testis. Treatment with radish and/or cress oil prior to BaP injection succeeded in reducing the germ cell genotoxicity as indicated by the decrease in DNA damage, 8-OHdG levels, sperm abnormalities, LPO level and increased sperm counts, motility and GSH content. Moreover, cress was found to be effective than radish and the combined treatment was more effective than the single treatment. It could be concluded that, pretreatment with radish and/or cress improved the epididymal sperm quality and reduced the genotoxicity and DNA damage induced by BaP, thereby declaring the protective role of radish and cress. [Copyright &y& Elsevier]

Background and objective The coal-fired pollution in Xuanwei area has been considered to be local main reason for high incidence of female lung cancer. The aim of this study is to explore the expression of PAH-DNA adducts in lung tissues of Xuanwei female lung cancer patients and to explore the relationship between the large number of coal-fired pollution PAHs materials and the high incidence of Xuanwei female lung cancer. Methods We totally collected each 20 cases of Xuanwei female lung cancer patients, Xuanwei male lung cancer patients, Non-Xuanwei female lung cancer patients and collect each 10 cases of Xuanwei, Non-Xuanwei female patients with benign lung lesions. The cancer tissues, adjacent cancer tissues and normal lung tissues were collected in lung cancer patients and only the normal tissues were collected in benign lung lesion patients. There were total 80 cases and 200 tissues. Immunofluorescence was used to detect the expression of PAHDNA adducts in each group. Image pro-plus 6.0 software was used to analyze the images and part quantified analysis. SPSS 13.0 statistical software was used to analyze the data. Results The positive expression of PAH-DNA adducts in lung cancer tissues, adjacent cancer tissues and normal lung tissues of Xuanwei female lung cancer patients were 90%, 80% and 65%. They were higher than the positive expression of PAH-DNA adducts in Xuanwei male lung cancer patients (35%, 30%, 30%) and Non- Xuanwei female lung cancer patients (20%, 15%, 10%)(P<0.01). The expressions in lung tissues of Xuanwei female benign lung lesion patients (positive expression is 70%) were higher than it in Non-Xuanwei female benign lung lesion patients (positive expression is 10%). With the direction changing from cancer tissues, adjacent cancer tissues to normal lung tissues, the expressions of PAH-DNA adducts were decreased but had no statistical difference (P>0.05). Conclusion The expressions of PAHDNA adducts in lung tissues of Xuanwei female were higher than which in Xuanwei male and Non-Xuanwei female. [ABSTRACT FROM AUTHOR]

The article discusses a study which examines the reduction of β-Lactoglobulin's (BLG's) immunogenicity through its conjugation with the N-hydroxysuccinimide ester of the dextran-glycylglycine adduct (DG-ONSu). Findings of the study reveal that the conjugation significantly decreased the reactivity of BLG with anti-BLG antibodies and DG-BLG was immune to proteolytic enzymes. It concludes that DG-ONSu could be used to subdue the hypersensitivity in milk allergy.

Summary: The DNA-repair protein O6-methylguanine-DNA methyltransferase removes alkyl adducts from the O6-position of guanine. The adducts can mispair with T during DNA replication, resulting in a G-to-A mutation. Epigenetic inactivation of O6-methylguanine-DNA methyltransferase has been found in human neoplasia and is considered one of the implicated factors in chemoresistance. Sixty-two patients with soft tissue sarcomas were analyzed with regard to the status of O6-methylguanine-DNA methyltransferase protein expression status using immunohistochemistry and promoter hypermethylation of the MGMT gene using methylation-specific PCR. G-to-A transitions in codons 12 and 13 of the K-ras oncogene were investigated using PCR and direct automated sequencing analysis. A loss of O6-methylguanine-DNA methyltransferase expression was noted in 20 (32.3%) cases of 62 total soft tissue sarcomas. The MGMT promoter hypermethylation rate was 33.9% (21/62 cases). Of the 54 sarcomas evaluated, K-ras mutations were found in only 2 (3.7%) cases. Loss of O6-methylguanine-DNA methyltransferase expression and MGMT promoter hypermethylation showed a significant association with high American Joint Committee on Cancer stage, high French Federation of Cancer Centers grade, and aggressive behavior. On multivariate analysis, these were not an independently significant prognostic factors. However, when the group receiving chemotherapy was analyzed (n = 27), loss of O6-methylguanine-DNA methyltransferase expression was correlated with worse survival on multivariate analysis (P = .024). MGMT promoter hypermethylation status had a strong correlation with loss of O6-methylguanine-DNA methyltransferase expression (P = .000). Our results suggest that MGMT promoter hypermethylation and loss of O6-methylguanine-DNA methyltransferase expression tend to be associated with poor prognosis and that the loss of O6-methylguanine-DNA methyltransferase protein expression frequently occurs via MGMT promoter hypermethylation. However, MGMT promoter hypermethylation was not significantly associated with point mutations of K-ras at codons 12 and 13 in sarcomas. [Copyright &y& Elsevier]

Abstract: Nitrosodimethylamine (NDMA) is a carcinogenic compound present in tobacco smoke and food such as cured meat, smoked fish and beer. The O 6-methylguanine formed in human cord blood in mothers highly exposed to such products implicates NDMA exposure of the fetus. Dual recirculating human placental perfusion was used to get direct evidence of the transplacental transfer of NDMA and DNA adduct formation in perfused human placenta. Eleven placentas from normal full-term pregnancies were collected immediately after delivery and an isolated lobule was perfused with 1 or 5μM of 14C-NDMA with a reference substance, antipyrine (0.1mg/ml) added to the maternal circulation. Perfusate samples were collected from both maternal and fetal circulations every half an hour for the first two hours and once per hour from thereon. NDMA was analyzed by scintillation counting and antipyrine by high performance liquid chromatography. The transfer of NDMA was comparable to that of antipyrine and probably occurred through passive diffusion, with the concentrations in maternal and fetal sides equilibrating in 2–3h. No indication of any effect by efflux transporters on NDMA kinetics was noticed in the experiments utilizing Caco-2 or MDCK- MDCKII-MDR1 cell culture monolayer in a transwell system, either. Furthermore, no NDMA-DNA-adducts were found after the perfusions and no DNA-binding of NDMA was seen in in vitro incubations with human placental microsomes from 8 additional placentas. Thus, our study demonstrates that the human fetus can be exposed to NDMA from the maternal circulation. According to this study and the literature, NDMA is not metabolized in full-term human placenta from healthy non-smoking, non-drinking mothers. It remains to be studied whether NDMA concentrations high enough to evoke fetal toxicity can be obtained from dietary sources. [Copyright &y& Elsevier]

In this study, three different soils with contrasting features, spiked with 300mg benzo[a]pyrene (BaP)/kg dry soil, were incubated at 20°C and 60% water holding capacity for 540days. At different time points, BaP and DNA were extracted and quantified, and DNA adducts were quantified by 32P-postlabelling. After 540days incubation, 69.3, 81.6 and 83.2% of initial BaP added remained in Cruden Bay, Boyndie and Insch soils, respectively. Meanwhile, a significantly different amount of DNA–BaP adducts were found in the three soils exposed to BaP over time. The work demonstrates the concept that DNA adducts can be detected on DNA extracted from soil. Results suggest the technique is not able to directly reflect bioavailability of BaP transformation products. However, this new method provides a potential way to detect mutagenic compounds in contaminated soil and to assess the outcomes of soil remediation. [Copyright &y& Elsevier]