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Objective: Exposure to airborne metal nanoparticles causes detrimental health consequences and increases the risk of lung cancer in exposed humans. This study aimed to investigate the effects of metal nanoparticles on oxidative stress-mediated DNA damage and inflammation, both in humans exposed to metal nanoparticles and in human bronchial epithelial cells (BEAS-2B). Method: Effects of exposure to metal nanoparticles were studied in welders using a cross-over design. Concentrations of metals bound to nanoparticles were measured by a personal nanoparticle sampler and analyzed by ICP-MS. Blood and urine samples were collected to determine oxidative DNA damage and transcript expression of DNA damage-related genes. The mechanisms by which iron oxide nanoparticle (FeNP)-induced oxidative DNA damage, apoptosis, and induction of inflammatory genes were investigated in BEAS-2B cells. Results: FeNP is a major form of airborne metal nanoparticles, contributing to 79% of all toxic metals in welding fumes. Exposure to airborne FeNP in welders was positively associated with blood Fe concentrations. Welders exposed to metal nanoparticles without a protective mask had increased oxidative DNA damage, observed as reduced urinary 8-OHdG, which suggest a decrease in DNA repair capacity. This was in line with significantly decreased transcript expression of the DNA repair gene (OGG1) and anti-oxidative response gene (Nrf2), as well as increased expression of the inflammatory response gene (IL-6), compared with those observed in the same welders wearing protective masks. In the in vitro study, BEAS-2B cells treated with FeNP had a decrease in cell viability and an increase in ROS generation, 8-OHdG, and apoptosis activity (caspase3-7) in a dose-dependent manner. FeNP treatment downregulated the expressions of OGG1 and Nrf2 and upregulated the expressions of IL-6 and IL-8. Conclusion: Exposure to FeNP induces oxidative DNA damage and inflammation, and this may contribute to an increased risk of respiratory diseases and cancer development.

Inhalable particulate matter (PM) is a health concern, and people living in large cities such as Bangkok are exposed to high concentrations. This exposure has been linked to respiratory and cardiac diseases and cancers of the lung and brain. Throughout 2018, PM was measured in northern Bangkok near a toll road (13.87°N, 100.58°E) covering all three seasons (cool, hot and rainy). PM10 was measured in 24- and 72-h samples. On selected dates aerodynamic size and mass distribution were measured as 3-day samples from a fixed 5th floor inlet. Particle number concentration was measured from the 5th floor inlet and in roadside survey measurements. There was a large fraction of particle number concentration in the sub-micron range, which showed the greatest variability compared with larger fractions. Metals associated with combustion sources were most found on the smaller size fraction of particles, which may have implications for associated adverse health outcomes because of the likely location of aerosol deposition in the distal airways of the lung. PM10 samples varied between 30 and 100 μg m−3, with highest concentrations in the cool season. The largest metal fractions present in the PM10 measurements were calcium, iron and magnesium during the hot season with average airborne concentrations of 13.2, 3.6 and 2.0 μg m−3, respectively. Copper, zinc, arsenic, selenium, molybdenum, cadmium, antimony and lead had large non-crustal sources. Principal component analysis (PCA) identified likely sources of the metals as crustal minerals, tailpipe exhaust and non-combustion traffic. A health risk analysis showed a higher risk of both carcinogenic and non-carcinogenic health effects in the drier seasons than the wet season due to ingestion of nickel, arsenic, cadmium and lead. Graphical abstract

Graphical abstract The effects of pyridoxine deficiency and benzene inhalation exposure (0 or 100 ppm) on hepatic CYP2E1 protein expression (A) and activity (B) in control (CD) and pyridoxine-deficient (PD) B6C3F1 mice. (a, b Significantly different from CD-0 controls at ap < 0.05 and bp < 0.001, respectively; c Significantly different from PD-0 controls at p < 0.05)., Highlights • Modifying effects of pyridoxine deficiency on benzene toxicity were assessed in B6C3F1 mice. • The mice were fed either a pyridoxine-deficient diet or control diet. • Pyridoxine deficiency was combined with nose-only benzene inhalation exposure (100 ppm). • Pyridoxine deficiency and benzene inhalation led to lower body, thymus and spleen weights. • The treatment combination also led to higher hepatic CYP2E1 protein expression and activity., Pyridoxine is a co-factor in many enzymatic reactions and impacts of deficiency have been observed in affected populations. A possible modifying effect of pyridoxine deficiency on benzene toxicity was assessed in male B6C3F1 mice fed either a pyridoxine-deficient diet or a control diet. This treatment was combined with benzene inhalation exposure (100 ppm) or no benzene treatment. Pyridoxine-deficient mice exposed to 100 ppm benzene had significantly lower body, thymus and spleen weights. While total white blood cell counts, percentage of lymphocytes, hematocrit and hemoglobin levels were lower, the percentage of neutrophils was significantly higher in deficient and benzene-exposed mice compared to non-exposed controls. Hepatic CYP2E1 protein expression and activity in the deficient and exposed mice were also significantly higher compared to the non-exposed controls. A significant correlation between CYP2E1 activity and several hematological parameters was observed. These results demonstrated that pyridoxine deficiency significantly impacted benzene-induced hematotoxicity. Moreover, the observed agonistic effect of pyridoxinedeficiency and benzene inhalation exposure on CYP2E1 would seem to indicate an involvement of metabolism, but this needs to be further assessed.

Inhalable particulate matter (PM) is a health concern, and people living in large cities such as Bangkok are exposed to high concentrations. This exposure has been linked to respiratory and cardiac diseases and cancers of the lung and brain. Throughout 2018, PM was measured in northern Bangkok near a toll road (13.87°N, 100.58°E) covering all three seasons (cool, hot and rainy). PM

DNA methylating agents are abundant in the environment and are sometimes used in cancer chemotherapy. They react with DNA to form methyl-DNA adducts and byproduct lesions that can be both toxic and...

Following publication of the original article [1], the author reported that incorrect version of Tables 1, 3, 5 and 6 were published.

Polybrominated Diphenylethers (PBDEs) were used as flame-retardants in various building materials, plastic and other polymers, airplanes, electronics etc. All or some of their congeners have been already banned in many countries, due to their persistency and adverse health effects. In this study, we are focusing on the e-wastes as a source of emission of PBDEs in ambient air during reclamation processes. The ambient air particulate matter (PM) samples were collected at and near e-waste reclamation site in Bangkok, Thailand. Results showed the presence of various homologues viz: tri, tetra, penta, hexa, and hepta-PBDEs on both PM2.5 and Total Suspended Particle (TSP) samples. The comparison of samples as a function of distance from reclamation site indicated elevated levels of PBDEs in the close proximity to e-waste site. Interestingly, a shift in the congener pattern was observed with lower brominated PBDEs being more prevalent on nearby off-site samples as compared to the PM collected at the e-waste site. The total penta-PBDEs concentration is about double on e-waste site PM2.5 compared to control site samples. For TSP, tetra, penta, and hepta-PBDEs congeners are at higher concentrations at e-waste sites and its vicinity compared to reference sites. Overall, a clear trend can be observed indicating a debromination of PBDEs to more toxic tri and tetra congeners during reclamation process and PBDEs are being translocated from treated materials to ambient air PM. BDE 30 congener is identified as a specific marker of thermal reclamation processes of e-wastes as a most stable degradation product. This work indicates potential hazards related to the reclamation of e-wastes and remediation of sites containing PBDEs. In particular, thermal treatment methods can lead to congener transformation and increased emissions of more toxic lower-brominated congeners.

The contribution of NOx emissions and background O3 to the sources and partitioning of the oxidants [OX (= O3 + NO2)] at the Marylebone Road site in London during the 2000s and 2010s has been investigated to see the impact of the control measures or technology changes inline with the London Mayor's Air Quality Strategy. The abatement of the pollution emissions has an impact on the trends of local and background oxidants, [OX]L and [OX]B, decreasing by 1.4% per year and 0.4% per year, respectively from 2000 to 2019. We also extend our study to three roadside sites (Din Daeng, Thonburi and Chokchai) in another megacity, Bangkok, to compare [OX]L and [OX]B and their behavioural changes with respect to the Marylebone Road site. [OX]L and [OX]B at the Marylebone Road site (0.21[NOx] and 32 ppbv) are comparable with the roadside sites of Thailand (0.12[NOx] to 0.26[NOx] and 29 to 32 ppbv). The seasonal variation of [OX]B levels displays a spring maximum for London, which is due to the higher northern hemispheric ozone baseline, but a maximum during the dry season is found for Bangkok which is likely due to regional-scale long-range transport from the Asian continent. The diurnal variations of [OX]L for both London and Bangkok roadside sites confirm the dominance of the oxidants from road transport emissions, which are found to be higher throughout the daytime. WRF-Chem-CRI model simulations of the distribution of [OX] showed that the model performed well for London background sites when predicting [OX] levels compared with the measured [OX] levels suggesting that the model is treating the chemistry of the oxidants correctly. However, there are large discrepancies for the model-measurement [OX] levels at the traffic site because of the difficulties in the modelling of [OX] at large road networks in megacities for the complex sub grid-scale dynamics that are taking place, both in terms of atmospheric processes and time-varying sources, such as traffic volumes. For roadside sites in Bangkok, the trend in changes of [OX] is predicted by the model correctly but overestimated in absolute magnitude. We suggest that this large deviation is likely to be due to discrepancies in the EDGAR emission inventory (emission overestimates) beyond the resolution of the model.

Growing evidence suggests that arsenic exposure increases the risk of developing a variety of inflammation-associated chronic diseases and cancers. Our previous study revealed that increased transcript levels of inflammatory genes (i.e. COX2, EGR1, and SOCS3) coupled with hypomethylation of the promoter regions of these genes was associated with increased DNA damage in arsenic-exposed newborns through their early childhood. This study further investigated the ability of the methyl group donors, S-adenosyl methionine (SAM) and folic acid, to prevent promoter hypomethylation that results in decreased mRNA expression of inflammatory genes (COX2, EGR1, and SOCS3), and a reduction in arsenic-induced oxidative and nitrative DNA damage in human lymphoblast cells. Pretreatment with SAM (100 nM, 2 days) increased promoter methylation, reduced the mRNA levels of these inflammatory genes, and decreased both 8-hydroxydeoxyguanosine (8-OHdG) and 8-nitroguanine levels by 50% (p 0.01) in arsenic-treated cells. In addition, pretreatment with folic acid (10 μM, 7 days), a micronutrient, led to a significant increase in promoter methylation associated with the reduction in mRNA levels of these inflammatory genes and decreased levels of 8-OHdG and 8-nitroguanine by 80% and 90% (p 0.01), respectively, compared with arsenic treatment alone. Moreover, pretreatments with these methyl group donors increased mRNA expression of an antioxidant defense regulator (Nrf2) and DNA repair genes (hOGG1, XRCC1, and PARP1). This study shows for the first time that SAM or folic acid supplementation can prevent arsenic-induced oxidative and nitrative DNA damage. This suggests the potential use of SAM or folic acid for prevention of arsenic toxicity in human populations.

Inorganic arsenic (iAs) is a naturally occurring metalloid present in drinking water and polluted air exposing millions of people globally. Epidemiological studies have linked iAs exposure to the development of numerous diseases including cognitive impairment, cardiovascular failure and cancer. Despite intense research, an effective therapy for chronic arsenicosis has yet to be developed. Laboratory studies have been of great benefit in establishing the pathways involved in iAs toxicity and providing insights into its mechanism of action. However, the in vivo analysis of arsenic toxicity mechanisms has been difficult by the lack of reliable in vivo biomarkers of the effects of iAs. To resolve this issue we have applied the use of our recently developed stress reporter models to study iAs toxicity. The reporter mice Hmox1 (oxidative stress/inflammation; HOTT) and p21 (DNA damage) were exposed to iAs at acute and chronic, environmentally relevant, doses. We observed induction of the oxidative stress reporters in several cell types and tissues, which was largely dependent on the activation of transcription factor NRF2. We propose that our HOTT reporter model can be used as a surrogate biomarker of iAs-induced oxidative stress, and it constitutes a first-inclass platform to develop treatments in arsenicosis. Indeed, in a proof of concept experiment, the HOTT reporter mice were able to predict the therapeutic utility of the antioxidant N-acetyl cysteine in the prevention of iAs associated toxicity.

Airborne particulate matter is known to be deleterious to human health and exceeds exposure limits in many large cities. Some heavy metals and metalloids are known carcinogens and have been measured as constituents of PM in Bangkok air. There is growing interest in the sub-micron and ultrafine (< 100 nm) fractions due to their deeper penetration in the lung. Identifying distribution of metals over the size range can provide information on the metals source as well as providing information on the likely exposure to those particles.Three sites, owned and managed by the Thailand Pollution Control Department, were identified to provide contrasting particulate samples in a measurement campaign during 2018. The Ayutthaya site was located within the grounds of a school, 80 km to the north of Bangkok. The site was chosen as concentrations due to city traffic would be lower and could be considered a reference site. The Bang Phli site was situated in an industrial area 50 km to the south-east of Bangkok, in an area near industry. The Chok Chai site was in central Bangkok near to a busy road.At each site, three 3-day weekend and 3-day weekday gravimetric samples of size differentiated mass were drawn using an Electrical Low Pressure Impactor (ELPI; Dekati, Finland) over 12 size fractions in six different study visits. These were chosen to enable three measurements over the rainy season and three in the dry season. Each size fraction was weighed and then analysed by inductively coupled plasma mass spectroscopy to find the concentration of 17 elements (Mg, Al, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Se, Mo, Cd, Sb, Ba and Pb). The ELPI also measured particle number concentration at 1 Hz. The number concentration of aerosol was highest in the Chok Chai roadside site, and lowest in the Ayutthaya background site. Al concentration was the highest in all three locations, with an average concentration over all measurements of 1909, 1012 and 1576 ng m-3 in Ayutthaya, Bang Phli and Chok Chai respectively. Concentrations of Al, Cr, Mg and Fe were typically higher than 100 ng m-3 in all sites, Cu and Zn higher than 10 ng m-3 and the rest lower.The shape of the metal distributions was consistent across all three sites for specific metals. Mg, Al, Cr, Mo, Ni and Cu could be described as having a flat distribution across all measured size distributions V, Mn, Cd, Sb, Pb, Zn As and Se had a peak in the sub-micron range, while Fe, Ba and Co peaked above 1 µm.Some seasonal effects could be seen across all three locations, these included an increase in Al, Cr and Fe during four measurements in dry season (November, 2018). This was particularly observed at Ayutthaya, where total measurements of Al were between 4862 and 5961 ng m-3, when all other measurements were between 98 and 264 ng m-3, suggesting a strong local source.

The vertical atmospheric potential gradient is particularly affected by high aerosol loading in cities as the air’s conductivity is reduced through aerosol attachment of free ions. The reduction of ion concentrations decreases the conductivity and, as the air-earth current remains constant, the potential difference increases. Aerosol size distributions can be affected by the relative humidity dependent on the aerosol hygroscopicity, if an aerosol is sufficiently hygroscopic, it will grow as humidity increases. As larger aerosols are, in principle, more prone to effectively scavenge ions, an increase in relative humidity may increase the size of hygroscopic aerosols, decrease ion concentrations and hence increased measured potential gradient. Measurements of atmospheric potential gradient in Lisbon, Portugal, demonstrated an increase in potential gradient associated with increasing relative humidity (in the range 60-90%), mainly for wind directions corresponding to marine air.A JCI 131 field mill (Chilworth) and Maximet 500 (Gill) weather station were positioned on the roof of the University of Bristol School of Chemistry between May and September 2016. Particle number concentration was determined using a condensation particle counter (TSI 3010) with an upper limit of 10,000 particles cm-3. A dilution system was put in place to increase this range to 14,000 cm-3. The same field mill and weather station were used in Thailand. Measurements at 1 Hz (averaged to 1-minute samples) were taken on the roof of a 6-floor building, approximately 100 m from a busy toll road in Lak Si, northern Bangkok. Aerosol concentrations were taken with a Condensation Particle Counter (Grimm Aerosol Technik) at the same height. The measurement period began on March 8th 2018 after which there were 8 weeks of particle number count data.In the Bristol measurement between 50% and 80% relative humidity, the median potential gradient increased, but above this it sharply decreases, which may be due to disturbed weather at the highest humidities. Initial analysis of the relationship between relative humidity and potential gradient in Bangkok shows a decrease in median potential gradient as relative humidity increases. This may be due to a large proportion of traffic related aerosol which could be less hygroscopic, but the potential for effects of disturbed weather and traffic to mask hygroscopic effects will be considered.

As one of the largest waste streams, electronic waste (e-waste) production continues to grow in response to global demand for consumer electronics. This waste is often shipped to developing countries where it is disassembled and recycled. In many cases, e-waste recycling activities are conducted in informal settings with very few controls or protections in place for workers. These activities involve exposure to hazardous substances such as cadmium, lead, and brominated flame retardants and are frequently performed by women and children. Although recycling practices and exposures vary by scale and geographic region, we present case studies of e-waste recycling scenarios and intervention approaches to reduce or prevent exposures to the hazardous substances in e-waste that may be broadly applicable to diverse situations. Drawing on parallels identified in these cases, we discuss the future prevention and intervention strategies that recognize the difficult economic realities of informal e-waste recycling.

Cholangiocarcinoma (CCA) is a severe cancer with poor prognosis. The aim of the present study was to explore the expression of argininosuccinate synthetase (ASS), as well as the possibility of using pegylated arginine deiminase (ADI-PEG20) for the treatment of CCA. ASS expression was determined in CCA specimens from 40 patients in Thailand. Immunohistochemical detection of ASS and determination of the proliferative index, Ki-67, were carried out in paraffin-embedded sections of these specimens, as well as in two CCA cell lines, HuCCA and RmCCA-1, derived from CCA samples from patients in Thailand. In total, ~45% of the CCA specimens had low ASS expression, and the level of expression was significantly negatively associated with cell differentiation (P

Dichloromethane (DCM), a widely used chlorinated solvent, is classified by IARC (2017) as probably carcinogenic to humans. Exposure to DCM has been associated with increased incidence of cholangiocarcinoma (CCA) in humans. This study aimed to investigate how DCM could contribute to CCA development by investigating the effects of DCM on DNA damage and cell transformation in cholangiocytes (MMNK-1) and on metastatic potential as measured by invasion and cell migration in malignant CCA cell lines (HuCCA-1 and RMCCA-1). MMNK-1 cells treated with the non-cytotoxic concentration of DCM (25 μM, 24 h) significantly increased the levels of mutagenic DNA adducts including 8-hydroxydeoxyguanosine, 8-OHdG, (1.84-fold, p 0.01) and 8-nitroguanine (1.96-fold, p 0.01) and enhanced cell transformation by 1.47-fold (p 0.01). In addition, the expression of various genes involved in carcinogenesis, namely, NFE2L2 (antioxidative response), CXCL8 (inflammation), CDH1 (cell adhesion), MMP9 (tissue remodeling) and MKI67 (cell proliferation) were altered in cholangiocytes treated with DCM. When MMNK-1 cells were transformed by DCM, the expression of all the aforementioned genes was also increased. In malignant cell lines (HuCCA-1 and RMCCA-1), DCM treatment resulted in increased CXCL8 and MMP9 transcription and decreased CDH1 transcription accompanied by increased invasion and migration capabilities of these cells. Taken together, this study demonstrated that DCM exposure could be linked to the development of CCA.

Major progress has been made in improving the health of vulnerable populations, especially children and pregnant women in low and middle income countries after the launch of the Millennium Development Goals in 2000. While fewer children die, many now face the prospect of years lived with disability (YLD) from chronic non-communicable diseases (NCDs). The estimate for the total YLD for children under-5 years of age for South-East Asia was 2,780,104 in 2015. To improve the health outcomes for children globally, the World Health Organization’s Department of Public Health, Environment and Social Determinants of Health has designated a number of collaborating centres, each with differing areas of expertise. The collaborating centres have formed a network to address children’s environmental health (CEH) issues at the local, national, regional and international levels. However, many gaps in knowledge exist. To further this aim, the 1st Regional Workshop of South-East Asian Children’s Environmental Health was held at the Chulabhorn Research Institute, Bangkok, on 18th November 2016. The workshop was attended by three of WHO Collaborating Centres with representatives of five regional countries of Bhutan, India, Myanmar, Thailand and Vietnam. Workshops such as this one are designed to bring together researchers and policy makers from regionals areas to identify and close gaps in knowledge.

Early-life exposure to arsenic increases risk of developing a variety of non-malignant and malignant diseases. Arsenic-induced carcinogenesis may be mediated through epigenetic mechanisms and pathways leading to inflammation. Our previous study reported that prenatal arsenic exposure leads to increased mRNA expression of several genes related to inflammation, including COX2, EGR1, and SOCS3. This study aimed to investigate the effects of arsenic exposure on promoter DNA methylation and mRNA expression of these inflammatory genes (COX2, EGR1, and SOCS3), as well as the generation of 8-nitroguanine, which is a mutagenic DNA lesion involved in inflammation-related carcinogenesis. Prenatally arsenic-exposed newborns had promoter hypomethylation of COX2, EGR1, and SOCS3 in cord blood lymphocytes (p

DNA methylating agents are abundant in the environment and are sometimes used in cancer chemotherapy. They react with DNA to form methyl-DNA adducts and byproduct lesions that can be both toxic and mutagenic. Foremost among the mutagenic lesions is O(6)-methylguanine (m6G), which base pairs with thymine during replication to cause GC→AT mutations. The gpt delta C57BL/6J mouse strain of Nohmi et al. (Mol. Mutagen, 1996;28:465–70) reliably produces mutational spectra of many DNA damaging agents. In this work, mouse embryo fibroblasts (MEFs) were made from gpt delta C57BL/6J mice and evaluated as a screening tool to determine the qualitative and quantitative features of mutagenesis by N-methyl-N-nitrosourea (MNU), a direct-acting DNA alkylator that serves as a model for environmental N-nitrosamines, such as N-nitrosodimethylamine and therapeutic agents such as temozolomide. The DNA repair protein MGMT (O(6)-methylguanine DNA methyltransferase) protects against environmental mutagenesis by DNA methylating agents and, by removing m6G, limits the therapeutic potential of temozolomide in cancer therapy. The gpt delta MEFs were treated with MNU to establish dose-dependent toxicity. In parallel, MNU mutagenicity was determined in the presence and absence of the MGMT inhibitor AA-CW236 (4-(2-(5-(chloromethyl)-4-(4-(trifluoromethoxy)phenyl)-1H-1,2,3-triazol-1-yl)ethyl)-3,5-dimethylisoxazole). With and without the inhibitor, the principal mutagenic event of MNU was GC→AT, but more mutations were observed when the inhibitor was present. Evidence that the mutagenic lesion was m6G was based on mass spectral data collected using O(6)-methyl-d(3)-guanine as an internal standard; m6G levels were higher in AA-CW236 treated MEFs by an amount proportional to the higher mutation frequency seen in the same cells. This work establishes gpt delta MEFs as a versatile tool for probing mutagenesis by environmental and therapeutic agents and as a cell culture model in which chemical genetics can be used to determine the impact of DNA repair on biological responses to DNA damaging agents.

Background Growing evidence indicates that in utero arsenic exposures in humans may increase the risk of adverse health effects and development of diseases later in life. This study aimed to evaluate potential health risks of in utero arsenic exposure on genetic damage in newborns in relation to maternal arsenic exposure. Methods A total of 205 pregnant women residing in arsenic-contaminated areas in Hanam province, Vietnam, were recruited. Prenatal arsenic exposure was determined by arsenic concentration in mother’s toenails and urine during pregnancy and in umbilical cord blood collected at delivery. Genetic damage in newborns was assessed by various biomarkers of early genetic effects including oxidative/nitrative DNA damage (8-hydroxydeoxyguanosine, 8-OHdG, and 8-nitroguanine), DNA strand breaks and micronuclei (MN) in cord blood. Results Maternal arsenic exposure, measured by arsenic levels in toenails and urine, was significantly increased (p

Children are particularly vulnerable to environmental hazards because they receive higher doses of pollutants in any given environment and often do not have equitable access to social protection mechanisms such as environmental and health care services. The World Health Organization established a global network of collaborating centres that address children’s environmental health (CEH). The network developed a focus on low- and middle-income countries (LMICs) and is broadening its reach by conducting regional workshops for CEH. Objective: This paper reports on the outcomes of a workshop held in conjunction with the 17th International Conference (November 2017) of the Pacific Basin Consortium for Environment and Health, focused on the state of CEH in South and Southeast Asia as presented by seven countries from the region (India, Bangladesh, Nepal, Bhutan, Vietnam, Thailand, Sri Lanka). Workshop outcomes: Country reports presented at the meeting show a high degree of similarity with respect to the issues threatening the health of children. The most common problems are outdoor and household air pollution in addition to exposure to heavy metals, industrial chemicals, and pesticides. Many children still do not have adequate access to clean water and improved sanitation while infectious diseases remain a problem, especially for children living in poverty. Child labour is widely prevalent, generally without adequate training or personal protective equipment. The children now face the dual burden of undernutrition and stunting on the one hand and overnutrition and obesity on the other. Conclusion: It is evident that some countries in these regions are doing better than others in varying areas of CEH. By establishing and participating in regional networks, countries can learn from each other and harmonise their efforts to protect CEH so that all can benefit from closer interactions.

Inorganic arsenic (iAs) is a naturally occurring metalloid present in drinking water and polluted air exposing millions of people globally. Epidemiological studies have linked iAs exposure to the development of numerous diseases including cognitive impairment, cardiovascular failure and cancer. Despite intense research, an effective therapy for chronic arsenicosis has yet to be developed. Laboratory studies have been of great benefit in establishing the pathways involved in iAs toxicity and providing insights into its mechanism of action. However, the in vivo analysis of arsenic toxicity mechanisms has been difficult by the lack of reliable in vivo biomarkers of iAs’s effects. To address this issue we have applied the use of our recently developed stress reporter models to study iAs toxicity. The reporter mice Hmox1 (oxidative stress/inflammation; HOTT) and p21 (DNA damage) were exposed to iAs at acute and chronic, environmentally relevant, doses. We observed induction of the oxidative stress reporters in several cell types and tissues, which was largely dependent on the activation of transcription factor NRF2. We propose that our HOTT reporter model can be used as a surrogate biomarker of iAs-induced oxidative stress, and it constitutes a first-in-class platform to develop treatments aimed to counteract the role of oxidative stress in arsenicosis. Indeed, in a proof of concept experiment, the HOTT reporter mice were able to predict the therapeutic utility of the antioxidant N-acetyl cysteine in the prevention of iAs associated toxicity.

Cholangiocarcinoma (CCA) is a deadly cancer of the bile duct and is considered an incurable disease with no efficacious treatment option. CCA arises as a consequence of chronic inflammation and tissue damage to the biliary epithelium. Thus, one of the crucial characteristics of CCA is its tumor microenvironment high in stromal extracellular matrices (ECMs), especially collagen I. Herein, the direct impact of collagen I on intrahepatic CCA (iCCA) cell lines were investigated. Our data demonstrate that iCCA cells mainly interact with collagen I, while cholangiocyte cells preferentially binds to fibronectin in cell adhesion assays. Correspondingly, iCCA cell lines exhibit over 20 fold-upregulation of ITGA2 gene, which encodes collagen-binding integrin α2, when compared with non-cancerous cholangiocyte cells. Furthermore, the result from the GEO dataset of 92 iCCA patients demonstrate that ITGA2 gene expression in iCCA tumors is 13 folds greater than their adjacent normal tissues and is positively correlated with expressions of two isoforms of collagen I gene, COL1A1 and COL1A2. Collagen I is also sufficient to drive proliferation of iCCA cells in a serum-restricted condition and this effect is mediated by integrin α2 as proven by ITGA2 silencing or α2β1-selective inhibitor treatment. In contrast to round-shaped, multicellular colonies of iCCA cells in clonogenic assays, iCCA colonies exhibit migratory phenotypes in the presence of collagen I. Likewise, this phenotype can be inhibited by α2β1-selective inhibitor treatment. Taken together, these data suggest that stromal collagen I could be one of the tumor microenvironmental factors directly facilitating iCCA progression. Thus, targeting the integrin α2-collagen I axis could be a promising therapeutic strategy for combating this cancer. Citation Format: Chotirat Rattanasinchai, Panida Navasumrit, Mathuros Ruchirawat. Integrin α2-collagen I axis promotes proliferative and migratory phenotypes in intrahepatic cholangiocarcinoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3964.

Paraquat (1,1′-dimethyl, 4,4′-bipyridinium dichloride; PQ), a widely used herbicide, is toxic to mammals through ingestion, inhalation and skin contact. Epidemiological data suggest that PQ is also mutagenic and carcinogenic, especially in high doses. The toxic and mutagenic properties of PQ are attributed to the ability of the molecule to redox-cycle, which generates reactive oxygen species (ROS) and subsequent oxidative stress. ROS also cause oxidative DNA damage such as 8-oxoguanine (8OG), a mutagenic base that, when replicated, causes G to T transversion mutations. The present study employed the CHO-derived cell line AS52 to quantify the mutagenic properties of low doses of PQ. By containing a functional, chromosomally-integrated copy of the bacterial gpt gene, AS52 cells a facile system for evaluating the mutagenic properties of genotoxicants. To bolster the sensitivity of this system for detecting mutagenesis of weak mutagens like PQ, and to provide a tool for mechanistic evaluation of the mutagenic process, we constructed a new AS52-derived cell line defective for 8OG DNA repair. Specifically, we employed CRISPR-Cas9 technology to knock out 8-oxoguanine DNA glycosylase (OGG1) and MUTYH glycosylase, two key enzymes involved in the base excision repair of 8OG. The double knock-out (DKO) AS52 cells were found to be more sensitive to PQ toxicity than the parental (WT) AS52 cell line. They experienced higher levels of ROS, which translated into more DNA double-strand breaks, which explained the PQ toxicity. The increased ROS levels also led to more 8OG genomic accumulation, and a higher level of mutations in the DKO cells, suggesting that PQ mutagenesis is mediated primarily by 8OG genomic accumulation. Consistent with this view, antioxidant co-treatment lowered induced cellular ROS and PQ-induced mutagenesis. Taken together, our data demonstrate the strong protective role of OGG1 and MUTYH against PQ-induced mutagenesis. Moreover, our experiments establish the engineered OGG1 MUTYH AS52 cell line and associated methods as a versatile cellular system for studying in quantitative terms the mutagenesis of other agents, environmental or endogenous, that induce oxidative stress. -/- -/

Aflatoxin B[subscript 1] (AFB[subscript 1]) is one of the major risk factors for liver cancer globally. A recent study showed that sulforaphane (SF), a potent inducer of phase II enzymes that occurs naturally in widely consumed vegetables, effectively induces hepatic glutathione S-transferases (GSTs) and reduces levels of hepatic AFB[subscript 1]-DNA adducts in AFB[subscript 1]-exposed Sprague Dawley rats. The present study characterized the effects of SF pre-treatment on global gene expression in the livers of similarly treated male rats. Combined treatment with AFB[subscript 1] and SF caused reprogramming of a network of genes involved in signal transduction and transcription. Changes in gene regulation were observable 4 h after AFB[subscript 1] administration in SF-pretreated animals and may reflect regeneration of cells in the wake of AFB[subscript 1]-induced hepatotoxicity. At 24 h after AFB[subscript 1] administration, significant induction of genes that play roles in cellular lipid metabolism and acetyl-CoA biosynthesis was detected in SF-pretreated AFB[subscript 1]-dosed rats. Induction of this group of genes may indicate a metabolic shift toward glycolysis and fatty acid synthesis to generate and maintain pools of intermediate molecules required for tissue repair, cell growth and compensatory hepatic cell proliferation. Collectively, gene expression data from this study provide insights into molecular mechanisms underlying the protective effects of SF against AFB[subscript 1] hepatotoxicity and hepatocarcinogenicity, in addition to the chemopreventive activity of this compound as a GST inducer., National Institutes of Health (U.S.) (Grants ES016313, P30-ES002109, P01 ES006052, P30 ES003819, and P30 CA006973)

Argininosuccinate synthetase (ASS), a key enzyme to synthesize arginine is down regulated in many tumors including hepatocellular carcinoma (HCC). Similar to previous reports, we have found the decrease in ASS expression in poorly differentiated HCC. These ASS(-) tumors are auxotrophic for arginine. Pegylated arginine deiminase (ADI-PEG20), which degrades arginine, has shown activity in these tumors, but the antitumor effect is not robust and hence combination treatment is needed. Herein, we have elucidated the effectiveness of ADI-PEG20 combined with 5-Fluorouracil (5-FU) in ASS(-)HCC by targeting urea cycle and pyrimidine metabolism using four HCC cell lines as model. SNU398 and SNU387 express very low levels of ASS or ASS(-) while Huh-1, and HepG2 express high ASS similar to normal cells. Our results showed that the augmented cytotoxic effect of combination treatment only occurs in SNU398 and SNU387, and not in HepG2 and Huh-1 (ASS(+)) cells, and is partly due to reduced anti-apoptotic proteins X-linked inhibitor of apoptosis protein (XIAP), myeloid leukemia cell differentiation protein (Mcl-1) and B-cell lymphoma-2 (Bcl-2). Importantly, lack of ASS also influences essential enzymes in pyrimidine synthesis (carbamoyl-phosphate synthetase2, aspartate transcarbamylase and dihydrooratase (CAD) and thymidylate synthase (TS)) and malate dehydrogenase-1 (MDH-1) in TCA cycle. ADI-PEG20 treatment decreased these enzymes and made them more vulnerable to 5-FU. Transfection of ASS restored these enzymes and abolished the sensitivity to ADI-PEG20 and combination treatment. Overall, our data suggest that ASS influences multiple enzymes involved in 5-FU sensitivity. Combining ADI-PEG20 and 5-FU may be effective to treat ASS(-)hepatoma and warrants further clinical investigation.

The present study aimed to assess arsenic exposure and its effect on oxidative DNA damage and repair in young children exposed in utero and continued to live in arsenic-contaminated areas. To address the need for biological specimens that can be acquired with minimal discomfort to children, we used non-invasive urinary and salivary-based assays for assessing arsenic exposure and early biological effects that have potentially serious health implications. Levels of arsenic in nails showed the greatest magnitude of difference between exposed and control groups, followed by arsenic concentrations in saliva and urine. Arsenic levels in saliva showed significant positive correlations with other biomarkers of arsenic exposure, including arsenic accumulation in nails (r=0.56, P

About 70% of breast tumors express androgen receptors. In addition, there is clinical evidence suggesting that androgens can inhibit mammary epithelial proliferation. Vice versa, there is also significant evidence indicating that androgens can increase the risk of breast cancer via multiple mechanisms, e.g. direct conversion to estrogens that can bind to the estrogen receptor and thereby stimulate cell proliferation. We examined the effect of testosterone (T) and dihydroxytestosterone (DHT) on cell proliferation, pS2 and Ki-67 expression in three different breast cancer cell lines alone or in co-culture with primary human breast adipose fibroblasts (BAFs) obtained from breast cancer patients. In the co-cultures, T induced cell proliferation, pS2 and Ki-67 expression in the estrogen receptor positive (ER(+)) MCF-7 and T47D cells. This was not observed in the (ER(-)) MDA-MB-231 cells. The differences might be explained by the high expression of aromatase, which converts androgens to estrogens in BAFs followed by ER-mediated cell proliferation. In line with this absence of increased cell proliferation, pS2 and Ki-67 expression was observed in the presence of DHT, which is not a substrate for aromatase. In contrast, DHT caused a significant suppression of cell proliferation (68% and 38%), pS2 and Ki-67 expression in the (ER(+)) MCF-7 and T47D cells. More importantly, DHT decreased cell proliferation in (ER(-)) MDA-MB-231 cells by 38%. The results suggest that androgens that cannot be aromatized, like DHT, may provide a perspective for treatment of breast cancer patients, especially those with triple negative breast cancer.

This study investigated arsenic (As) concentrations in existing drinking water sources in Hanam province, Vietnam. Sand-filtered groundwater, piped water, raw groundwater, and a type of drinking water mostly sourced from rainwater (hereafter referred to as the “stored rainwater”) are commonly used for drinking purposes in this area. It was found that all water sources contained different levels of toxic As. The highest levels were found in raw groundwater, followed by sandfiltered water, piped water, and stored rainwater. More than 50% of the stored rainwater samples contained As levels above the WHO recommendation value. As such, the daily As uptake in local residents from this kind of stored rainwater may be larger than previously considered because they consume stored rainwater as an alternative drinking water source. Relatively high levels of As in the stored rainwater samples also suggested that residents possibly mix rain and groundwater in rainwater containers in order to meet their daily water demand.

Graphical abstract, Highlights • Depsidones are aromatase inhibitors in primary human breast adipose fibroblasts. • Depsidones may have pharmacotherapeutical relevance for breast cancer treatment. • Co-cultures of breast tumor and fibroblasts cells create a vivo realistic in vitro model for estrogen dependent breast cancer., Naturally occurring depsidones from the marine fungus Aspergillus unguis are known to have substantial anti-cancer activity, but their mechanism of action remains elusive. The purpose of this study was to examine the anti-aromatase activity of two common depsidones, unguinol and aspergillusidone A, in a co-culture system of human primary breast adipose fibroblasts and hormonal responsive T47D breast tumor cells. Using this in vitro model it was shown that these depsidones inhibit the growth of T47D tumor cells most likely via inhibition of aromatase (CYP19) activity. The IC50 values of these depisidones were compared with the aromatase inhibitors letrozole and exemestane. Letrozole and exemestane had IC50 values of respectively, 0.19 and 0.14 μM, while those for Unguinol and Aspergillusidone A were respectively, 9.7 and 7.3 μM. Our results indicate that among the depsidones there maybe aromatase inhibitors with possible pharmacotherapeutical relevance.

The aim of this study was to investigate prevalence and related factors of androgen receptor (AR) expression in Thai breast cancer patients. A descriptive study was done in 95 patients, who were admitted to Charoenkrung Pracharak Hospital, Bangkok (2011-2013). Statistical relationships were examined between AR protein expression, tumor status, and patient characteristics. Compared with those from Western countries, ethnic Thai patients were younger at age of diagnosis and had a higher proliferative index (high Ki-67 expression), which indicates unfavorable prognosis. In addition, 91% of the Thai breast tumors that were positive for any of the following receptors, estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) also expressed the AR protein, while in triple negative breast tumors only 33% were AR positive. ER and PR expression was positively related with AR expression, while AR expression was inversely correlated to Ki-67 expression. AR status was strongly correlated with ER and PR status in Thai patients. There is an inverse relationship between Ki-67 and AR, which suggests that AR may be a prognostic factor for breast cancer.

Emissions from petrochemical industries may contain toxic and carcinogenic compounds that can pose health risk to human populations. The scenario may be worse in developing countries where management of such exposure-health problems is typically not well-implemented and the public may not be well-informed about such health risk. In Thailand, increasing incidences of respiratory diseases and cancers have been reported for the population around a major petrochemical complex, the Map Ta Phut Industrial Estate (MTPIE). This study aimed to systematically investigate an exposure-health risk among these populations. One-hundred and twelve healthy residents living nearby MTPIE and 50 controls located approximately 40km from MTPIE were recruited. Both external and internal exposure doses to benzene and 1,3-butadiene, known to be associated with the types of cancer that are of concern, were measured because they represent exposure to industrial and/or traffic-related emissions. Health risk was assessed using the biomarkers of early biological effects for cancer and inflammatory responses, as well as biomarkers of exposure for benzene and 1,3-butadiene. The exposure levels of benzene and 1,3-butadiene were similar for both the exposed and control groups. This was confirmed by a non-significant difference in the levels of specific urinary metabolites for benzene (trans,trans-muconic acid, t,t-MA) and 1,3-butadiene (monohydroxy-butyl mercapturic acid, MHBMA). Levels of 8-hydroxydeoxyguanosine (8-OHdG) and DNA strand breaks between the two groups were not statistically significantly different. However, functional biomarkers, interleukin-8 (IL-8) expression was significantly higher (p0.01) and DNA repair capacity was lower (p0.05) in the exposed residents compared to the control subjects. This suggests that the exposed residents may have a higher risk for development of diseases such as cancer compared to controls. However, the increased expression of IL-8 and lower DNA repair capacity were not associated with recent and excessive exposure to benzene and 1,3-butadiene, which were at the similar levels as those in the controls. The data would indicate that previous exposure to the two chemicals together with exposure to other toxic chemicals from the MTPIE may be responsible for the elevated functional biomarkers and health risk. Further studies are required to determine which other pollutants from the industrial complex could be causing these functional abnormalities.

Pembakaran dupa yang merupakan bagian dari ritual agama dan budaya mayoritas komunitas Oriental, diketahui berpotensi menyebabkan efek berbahaya akibat emisi yang menghasilkan berbagai jenis polutan. Telah dilakukan identifikasi senyawa Polycylic Aromatic Hydrocarbons (PAHs) yang berasal dari emisi hasil pembakaran beberapa tipe dupa dalam sebuah ruang eksperimen. Studi ini dilakukan di Chulabhorn Research Institute, Thailand dengan tujuan untuk mengetahui tingkat emisi PAHs yang terikat dalam partikulat pada sampel-sampel dupa dari tiga negara (Indonesia, Thailand, dan Vietnam) yang dipilih secara acak. Dari hasil analisis PAHs menggunakan High Performance Liquid Chromatography dengan Fluorescence Detector (HPLC-FLD) diketahui bahwa komponen dominan dalam sampel dupa Indonesia dan Thailand adalah fluorenthane (Flu) dengan konsentrasi masing-masing 8.2±1.0 dan 3.5±0.5 mg/m3, sementara sampel Vietnam didominasi oleh komponen chrysene (CHR) (34.5±10.6 μg/m3). Sampel dupa Vietnam mengemisikan total PAHs ~5 kali lebih tinggi dari dupa Indonesia dan ~8 kali lebih tinggi dari dupa Thailand. Seluruh sampel mengemisikan Benzo[a]pyrene (BaP) dalam level serupa, meskipun konsentrasi dalam dupa Vietnam masih ~1.3 kali lebih tinggi dari dupa Indonesia dan ~1.8 kali dari dupa Thailand. Sementara untuk nilai BaP ekivalen, dupa Vietnam ~3.7 kali dan ~7kali lebih tinggi dari sampel Indonesia dan Thailand.

Background Millions of individuals worldwide, particularly those living in rural and developing areas, are exposed to harmful levels of inorganic arsenic (iAs) in their drinking water. Inorganic As exposure during key developmental periods is associated with a variety of adverse health effects, including those that are evident in adulthood. There is considerable interest in identifying the molecular mechanisms that relate early-life iAs exposure to the development of these latent diseases, particularly in relationship to cancer. Objectives This work summarizes research on the molecular mechanisms that underlie the increased risk of cancer development in adulthood that is associated with early-life iAs exposure. Discussion Epigenetic reprogramming that imparts functional changes in gene expression, the development of cancer stem cells, and immunomodulation are plausible underlying mechanisms by which early-life iAs exposure elicits latent carcinogenic effects. Conclusions Evidence is mounting that relates early-life iAs exposure and cancer development later in life. Future research should include animal studies that address mechanistic hypotheses and studies of human populations that integrate early-life exposure, molecular alterations, and latent disease outcomes. Citation Bailey KA, Smith AH, Tokar EJ, Graziano JH, Kim KW, Navasumrit P, Ruchirawat M, Thiantanawat A, Suk WA, Fry RC. 2016. Mechanisms underlying latent disease risk associated with early-life arsenic exposure: current research trends and scientific gaps. Environ Health Perspect 124:170–175; http://dx.doi.org/10.1289/ehp.1409360

Highlights • Unguinol and Aspergillusidone D inhibit cell viability at low μM concentrations. • These depsidones increase the amount of apoptotic cells in the MDA-MB-231 cell line. • Unguinol causes cell cycle arrest of MDA-MB-231 cells in the G2/M-phase. • Apoptosis and cell cycle arrest were seen at clinically high concentrations (>60 μM)., There is an ongoing search for new compounds to lower the mortality and recurrence of breast cancer, especially triple-negative breast cancer. Naturally occurring depsidones, extracted from the fungus Aspergillus, are known for their wide range of biological activities such as cytotoxicity, aromatase inhibition, radical scavenging, and antioxidant properties. Research showed the potential of depsidones as a treatment option for hormone receptor-positive breast cancer treatment, yet its effects on hormone receptor-negative breast cancer are still unkown. This study, therefore, investigated the potential of two depsidones (Unguinol and Aspergillusidone D) to induce apoptosis, cell cycle arrest and cytotoxicity, and reduce cell proliferation in the triple-negative MDA-MB-231 breast cancer cell line. Results were compared with the effects of the cytostatic drug doxorubicin, antimitotic agent colchicine and endogenous hormones 17β-estradiol, testosterone and dihydrotestosterone. The cytostatic drugs and hormones affected the MDA-MB-231 cell line comparable to other studies, showing the usefulness of this model to study the effects of depsidones on a triple-negative breast cancer cell line. At sub μM levels, Unguinol and Aspergillusidone D did not influence cell proliferation, while cell viability was reduced at concentrations higher than 50 μM. Both depsidones induced apoptosis, albeit not statistically significantly. In addition, Unguinol induced cell cycle arrest in MDA-MB-231 cells at 100 μM. Our research shows the potential of two depsidones to reduce triple-negative breast cancer cell survival. Therefore, this group of compounds may be promising in the search for new cancer treatments, especially when looking at similar depsidones.

Incense smoke is a potential hazard to human health due to various airborne carcinogens emitted from incense burning. This study aimed to evaluate the potential health effects of exposure to benzene, 1,3-butadiene, and polycyclic aromatic hydrocarbons (PAHs) emitted from incense smoke in temple workers. Exposure and health risks were assessed through the measurement of ambient exposure as well as through the use of biomarkers of exposure and early biological effects. Ambient air measurement showed that incense burning generates significantly higher levels of airborne benzene (P

Exposure to low-dose gamma radiation is common in certain occupations but the biological and health effects from such exposure remain to be determined. The aim of this study was to investigate the effects of low-dose gamma radiation on DNA damage, chromosomal aberration and DNA repair gene expressions in whole blood and peripheral lymphocytes. The study revealed a dose-dependent effect of gamma radiation on DNA damage. Significant increases in DNA strand breaks and oxidative base damage, determined as formamidopyrimidine-DNA-glycosylase (FPG)-sensitive sites, were observed at absorbed doses of 5 and 10cGy, respectively. However, gamma radiation at doses up to 500cGy did not significantly increase the level of 8-oxo-7, 8-dihydro-2'-deoxyguanosine (8-oxodG) determined by HPLC with electrochemical detection (HPLC-ECD). Gamma radiation as low as 5cGy caused chromosomal aberrations determined as dicentric and deletion frequencies. This finding is significant since the genotoxic effects of gamma radiation can be observed even at a low dose of 5cGy. Furthermore, gamma radiation decreased the mRNA expression of both hOGG1 and XRCC1 repair genes determined by reverse transcriptase-polymerase chain reaction (RT-PCR), with a significant decrease of expression being observed at 20cGy. The expression levels of hOGG1 and XRCC1 mRNA were inversely correlated with the levels of FPG-sensitive sites and DNA strand breaks. The finding of decreased expression levels for hOGG1 and XRCC1 in gamma-irradiated lymphocytes has not been reported elsewhere. Our observations suggest that the genotoxic effects of gamma radiation may be due to a combination of DNA-damaging effects and reduced DNA repair capacity, and may explain the significant increase in health risk from high doses of ionizing radiation.

Air pollution is a serious problem in many countries in Southeast Asia, particularly in major metropolises with high levels of traffic congestion generating significant amounts of genotoxic substances. The contribution of such environmental exposure to children's illnesses, such as respiratory diseases and cancer, is a public health concern. Inner-city children may have higher levels of exposure to genotoxic substances in the air than those living in rural areas. This study was conducted in Bangkok, where ambient levels of polycyclic aromatic hydrocarbons (PAHs) and benzene are relatively high. Bangkok school children were exposed to total PAHs at about sixfold higher levels than those in rural areas, with levels of urinary 1-hydroxypyrene (1-OHP) also being significantly higher. PAH-DNA adduct levels in lymphocytes were fivefold higher in Bangkok children. Benzene exposure in Bangkok school children was more than twofold higher than the levels measured in children from the rural areas. This is in agreement with the biomarkers of internal dose, that is, blood benzene and urinary trans, trans-muconic acid (t,t-MA) levels. The potential health risks from exposure to PAHs and benzene were assessed through the use of DNA damage and DNA repair capacity as markers of early biological effect. DNA strand breaks were significantly higher in Bangkok school children, while DNA repair capacity was significantly lower. It appears that children in major cities in developing countries may have an increased health risk for the development of certain diseases, such as cancer due to exposure to genotoxic substances in their environment.

Exposure to benzene in air is a concern in Thailand, particularly since it was observed that the incidence of blood-related cancers, such as leukemia and lymphoma, has increased in the past few decades. In Bangkok, the mean atmospheric levels of benzene on main roads and in schools were 33.71 and 8.25 ppb, respectively, while in gasoline service stations and petrochemical factories the mean ambient levels were 64.78 and 66.24 ppb, respectively. Cloth vendors (22.61 ppb) and grilled-meat vendors (28.19 ppb) working on the roadsides were exposed to significantly higher levels of benzene than the control group (12.95 ppb; p0.05). Bangkok school children (5.50 ppb) were exposed to significantly higher levels of benzene than provincial school children (2.54 ppb; p0.01). Factory workers (73.55 ppb) and gasoline service attendants (121.67 ppb) were exposed to significantly higher levels of benzene than control workers (4.77 ppb; p0.001). In accordance with the increased benzene exposures, levels of urinary trans,trans-muconic acid (MA) were significantly increased in all benzene-exposed groups. In school children, the levels of MA were relatively high, taking into account the much lower level of exposure. Blood benzene levels were also significantly increased in Bangkok school children (77.97 ppt; p0.01), gasoline service attendants (641.84 ppt; p0.05) and factory workers (572.61 ppt; p0.001), when compared with the respective controls. DNA damage, determined as DNA strand breaks, was found to be elevated in gasoline service attendants, petrochemical factory workers, and Bangkok school children (p0.001). The cytogenetic challenge assay, which measures DNA repair capacity, showed varying levels of significant increases in the numbers of dicentrics and deletions in gasoline service attendants, petrochemical factory workers and Bangkok school children, indicating a decrease in DNA repair capacity in these subjects.

Early life exposure to inorganic arsenic is associated with a wide range of malignant and chronic disease outcomes in humans. Prenatal arsenic exposure may give rise to adverse effects on child health and development as arsenic readily passes through the placenta in human beings. The impact of maternal arsenic exposure on fetal gene expression was conducted in pregnant women living in Southern Thailand. Arsenic exposed newborns had significantly higher levels of arsenic in cord blood, and a set of genes associated with numerous biological pathways, including cell signaling, apoptosis, inflammatory and stress response. A slight increase in promoter methylation of p53 in cord blood lymphocytes which correlated with arsenic accumulation in nails was observed in these exposed newborns. A follow-up study on these exposed children showed a significant increase in oxidative DNA damage, measured as 8-hydroxydeoxyguanosine (8-OHdG) in saliva. In addition, levels of urinary 8-OHdG excretion and salivary hOGG1 expression were significantly decreased in exposed children suggesting a defect in repair of 8-OHdG in arsenic-exposed children. Our study indicates that prenatal arsenic and continued exposure through early childhood can trigger various genetic and epigenetic alterations that may lead to disease development later in life.