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Objective: To explore the role of nuclear transcription factor E2-related factor 2(NRF2)-mediated reductive stress in arsenite induced malignant transformation in human keratinocytes., Methods: HaCaT cells and fluorescent labeled mitochondrial glutathione HaCaT cells(Mito-Grx1-roGFP2 HaCaT) were cultured to 35 passages in medium containing 0.0 and 1.0 μmol/L NaAsO_2 to establish a model of malignant transformation of cells. Cellular and mitochondrial reduced glutathione/oxidized glutathione(GSH/GSSG) and reduced coenzyme II/oxidized coenzyme II(NADPH/NADP~+) ratios were measured in HaCaT cells. Cell doubling time, cell migration ability, soft agar clone formation ability and GSH/GSSG at different times in the 0 passage, the early stage(1st, 7th and 14th passages) and later stage(21st, 28th and 35th passages) were measured in Mito-Grx1-roGFP2 HaCaT cells. NaAsO_2 induced malignant transformation cells were transfected with NRF2 siRNA, and detected the expression level of NRF2 and the redox-related indexes and malignant transformation indexes., Results: Compared with the control group, the GSH/GSSG ratio in 1.0 μmol/L NaAsO_2 treated HaCaT cells significantly decreased in the 1st and 7th generations, but significantly increased after the 21st generation, and the NADPH/NADP~+ ratio significantly increased in the 1st, 14th, 21st, 28th and 35th generations; The levels of GSH/GSSG in mitochondria significantly increased from 1st to 35th generation, and the levels of NADPH/NADP~+ in mitochondria significantly increased at 1st, 7th, 21st, 28th and 35th generation. After continuous treatment of Mito-Grx1-roGFP2 HaCaT cells with 0.0 or 1.0 μmol/L NaAsO_2 to 35 passages, the doubling time of cells treated with 1.0 μmol/L NaAsO_2 was significantly shortened, the cell migration rate was increased greatly, and more clones with larger volumes than the control cells formed. The GSH/GSSG ratio in mitochondria of Mito-Grx1-roGFP2 HaCaT cells showed a significant decrease in the 1st generation and increased from the 7th generation onwards(all P<0.05). After transfection of NaAsO_2 treated cells with NRF2 siRNA, the levels of hydrogen peroxide and superoxide increased compared with the siRNA controls. The levels of cell and mitochondrial NADPH/NADP~+ and GSH/GSSG decreased and the level of mitochondrial GSH/GSSG in Mito-Grx1-roGFP2 HaCaT cells decreased. Cell doubling time increased, cell migration rate and soft agar clone formation ability decreased(all P<0.05). The malignant phenotype was reversed., Conclusion: In the early stage(1st, 7th and 14th passages) of NaAsO_2 treated HaCaT cells, oxidative stress occurred with continuous high NRF2 expression. Later(21st, 28th and 35th passages), NRF2 induced reductive stress, leading to malignant transformation.

Objective: To systematic evaluate the association between maternal arsenic exposure and preterm birth., Methods: A literature search was conducted through Pubmed, Web of Science, Embase, China Knowledge Network(CNKI), WanFang Data, Vip Chinese Journal Service Platform(VIP) with a time frame of November 2022 from the beginning of database construction. Meta-analysis of dichotomous variables was performed using Stata MP15 software, and a random or fixed effects model was chosen for the meta-analysis based on the heterogeneity result, with the ratio of ratios(OR) as the effect indicator; subgroup analysis was used to find characteristic changes; funnel plots were used to evaluate publication bias., Results: A total of 15 papers with a sample size of(n=9 892 256 279), 10 prospective cohort studies, 3 retrospective cohort studies, and 2 cross-sectional studies, were included in 6 Chinese and 9 English papers. By Meta-analysis, the combined OR of preterm birth outcome was 1.06(95%CI 1.03-1.09); the result of subgroup analysis by exposure factors and region, the combined OR(95%CI) of hair, blood, urine, drinking water, and placenta were 0.97(0.56-1.69), 1.40(1.22-1.60), 1.04(0.93-1.17), 1.14(1.04-1.24) and 0.69(0.07-6.38). The combined OR(95%CI) were 1.17(1.04-1.31), 1.10(1.05-1.14), 0.69(0.07-6.38) and 1.17(1.01-1.36) for Asia, Americas, Europe and Africa, respectively. For subgroup analysis based on study type, the combined OR(95%CI) was 1.16(1.05-1.28), 1.01(1.01-1.02) and 1.65(0.73-3.74) for prospective cohort studies, retrospective cohort studies, and cross-sectional studies, respectively., Conclusion: Maternal arsenic exposure may contribute to the occurrence of preterm birth, and drinking water arsenic levels may be an important indicator for assessing human arsenic exposure and risk of causing preterm birth.

As arsenic widely exists in nature and has been used in the pharmaceutical preparations, the traditional Chinese medicine(TCM) with arsenic include realgar(As_2S_2 or As_4S_4), orpiment(As_2S_3), and white arsenic(As_2O_3). Among the above representative medicine, the TCM compound formulas with realgar are utilized extensively. Just in Chinese Pharmacopoeia(2020 edition), there are 37 Chinese patent medicines including realgar. The traditional element analysis focuses on the detection of the total amount of elements, which neglects the study on the speciation and valence of elements. The activity, toxicity, bioavailability, and metabolic pathways of arsenic in vivo are closely related to the existence of its form, and different forms of arsenic have different effects on organisms. Therefore, the study on the speciation and valence of arsenic is of great importance for arsenic-containing TCMs and their compound formulas. This paper reviewed four aspects of the speciation and valence of arsenic, including property, absorption and metabolism, toxicity, and analytical assay.

Chronic kidney disease (CKD) is suffered progressive loss of kidney function lasting more than 3 months and is classified according to the degree of kidney damage (level of proteinuria) and the decreased glomerular filtration rate (GFR). The most severe form of CKD is end-stage renal disease. The prevalence of CKD is high with fast growth rate and the disease burden has become increasingly serious. CKD has become an important public health problem threatening human health. The etiology of CKD is complex. In addition to genetic factors, environmental factors are an important cause of CKD. With the development of industrialization, environmental metal pollution has become increasingly severe, and its impact on human health has received widespread attention. A large number of studies have shown that metals such as lead, cadmium, and arsenic can accumulate in the kidney, which can cause damage to the structure and function of the kidney, and play an important role in the development of CKD. Therefore, summarizing the epidemiological research progress in the relationship between arsenic, cadmium, lead, and other metal exposures and kidney diseases can provide new ideas for the prevention and control of kidney diseases caused by metal exposure.

Arsenic is a non-metallic element, and the International Agency for Research on Cancer has identified arsenic and its compounds as carcinogens. Arsenic and its compounds can be absorbed through the respiratory tract, skin and digestive tract, distributed in the liver, kidney, lung and skin, and cause damage. Non-coding RNAs are closely related to arsenic-induced nervous system disorders, cell necrosis, reproductive toxicity, and carcinogenesis. In recent years, the network regulation of microRNAs (miRNAs) , long non-coding RNAs (lncRNAs) , and circular RNAs (circRNAs) among non-coding RNAs in various diseases induced by arsenic has become a new research field. This paper summarizes the existing scientific research results, and expounds the mechanism of miRNAs, lncRNAs and circRNAs in arsenic toxicity, and provides basic data and theoretical basis for the prevention and treatment of arsenic poisoning.

Devitalization has been widely used in the root canal therapy of primary and permanent teeth in China more than ten years ago. With the development of local anesthetic drugs and injection technologies, this treatment method with high potential risks has been gradually abandoned. However, a questionnaire survey targeted all the participants at the 2018 China Pediatric Dentistry Conference showed that the devitalizer utilization proportion was still as high as 38.1% (383/1 005), even though the ratio was much lower than 75.5% (105/139) in 2003. These doctors had pay more attention to tissue burn caused by devitalizer marginal leakage or direct leakage, and know how to identify and handle with devitalizer burn. Devitalizers were usually made of arsenic trioxide, metal arsenic or paraformaldehyde, which have cytotoxicity, allergenicity, mutagenicity, carcinogenicity, and teratogenic effects on animals. Marginal leakage of devitalizers have high risks of causing soft and hard tissue necrosis. Most of the dentists have an understanding of the potential damages of arsenic containing devitalizers, so they will choose parafor maldehyde with relatively less toxicity. Paraformaldehyde has a certain self limitation, and there are few cases reported, so some dentists lack of vigilance. Paraformaldehyde can also causes tissue necrosis if leakage happens, and the treatment methods are similar to that of arsenic containing devitalizers. When handling with devitalizers burn, the necrosed soft and hard tissue, for example gingiva, alveolar bone or teeth that cannot keep, must be completely removed until fresh blood appears, then rinse with large amount of saline and seal with iodoform gauze. This paper described two cases of devitalizer burn during the root canal treatment of primary molars, both of the doctors failed to identify the devitalizer burn symptoms in the early stage, thus didn't do proper treatments immediately after burning. Resulting in the necrosis of large area of gingiva and alveolar bone, loss of primary molars and permanent tooth germs 1-2 months after devitalizer burn. This paper reported these two cases in detail in order to warn dentists the high risks of using any kind of devitalizers, help them learn how to identify and treat devitalizer burn, and remind them to stop using devitalizers as soon as possible.

Heavy metal is an important environmental stress that threatens water quality and ecological health of surface waters. Therefore, it is vital to identify the responses of lake community to long-term pollution for sustainable ecological restoration of polluted lakes. From June 2017 to March 2018, we conducted a seasonal survey of phytoplankton and environmental factors in Datun Lake, which had a decadal history of tailing-related arsenic contamination. Consistent with results from previous studies, phytoplankton were dominated by As-tolerant taxa such as Cyanophyta. Results of the analysis of similarities and analysis of variance showed that there were significant temporal variations in phytoplankton community structure and biomass, but without spatial variation. Results of the Pearson correlation analysis demonstrated that the total phytoplankton biomass was positively related to lake-water soluble orthophosphate and arsenic, which was consistent with the differential effect of arsenic on algae growth ( e.g . promotion at low concentration and suppression at high concentration). The increases of phosphate might alleviate the toxic impacts of arsenic on phytoplankton. Redundancy analysis showed that the soluble nutrients and arsenic were significant factors driving phytoplankton community variations. The results of variation partitioning demonstrated that nutrients and water temperature explained 17.6% and 3.8% of community variations, respectively, with strong interaction with arsenic (15.1%). Arsenic did not affect phytoplankton community assembly, indicating that the dominant algae were tolerant to arsenic and thus highly insensitive to the arsenic stress. Therefore, the seasonal variations of phytoplankton dominated by As-tolerant algae in Datun demonstrated that the low-As promotion effect on phytoplankton should be considered in ecological restoration of polluted lakes.

Objective To investigate the effects of inorganic arsenic exposure on the differentiation of renal CD4 + T lymphocytes and the possible mechanism. Methods Female C57BL/6 mice were randomly divided into control group, (2.5, 5, 10) mg/kg NaAsO 2 exposure groups, 10 mice in each group. As was administered once intragastrically for 24 hours, and control mice were treated with normal saline. Real-time fluorescence quantitative PCR was used to detect T helper type 1 (Th1) cell-specific transcription factor T-box expressed in T cells (T-bet) and IFN-γ, Th2 cell-specific transcription factor GATA-binding protein 3 (GATA3) and interleukin 4 (IL-4), Th17 cell-specific transcription factor retinoic acid related orphan nuclear receptor γt (ROR-γt) and cytokine IL-22, regulatory T cells (Tregs)-specific transcription factor forkhead box P3 (FOXP3) and cytokine transforming growth factor-β (TGF-β) mRNA levels. We used commercial kits to detect catalase (CAT) activity and total antioxidant capacity (T-AOC) in serum as well as renal malondialdehyde (MDA) and superoxide dismutase (SOD). Results Compared with the control group, the body mass, renal mass and kidney index of the mice in all arsenic-treated groups have no significant changes. The levels of the master transcription factors T-bet, GATA3, ROR-γt and FOXP3 as well as related cytokines IFN-γ, IL-4, IL-22 and TGF-β of Th1, Th2, Th17 cells and Tregs decreased in the arsenic-treated groups. Serum CAT activity and T-AOC level in the arsenic-treated mice dropped greatly. In addition, arsenic markedly increased renal MDA level while decreased SOD activity. Conclusion Inorganic arsenic exposure can suppress renal T cell subpopulation function and induce renal oxidative injure.

Objective: To explore the association of arsenic with unexplained recurrent spontaneous abortion (URSA). Methods: A case-control study was conducted to select URSA patients who were admitted to the Beijing Maternal and Child Health Care Hospital affiliated to Capital Medical University from April to October 2018 as a case group. Women who had a normal pregnancy in the Family Planning Department of the hospital but volunteered to have an abortion were selected as a control group. The case and control group were paired in a 1: 1 ratio. The inclusion criteria of the case group were patients with newly diagnosed recurrent spontaneous abortion who had clinically confirmed more than 2 spontaneous abortions and had 20 weeks prior to pregnancy, excluding patients with recurrent spontaneous abortion caused by abnormal blood coagulation (anti-phospholipid antibody positive), abnormal physiological anatomy (B-ultrasound), abnormal immune factors (anti-nuclear antibody positive, anti-cardiolipin antibody, etc.), genetic chromosomal abnormalities (karyotype analysis) and pathogenic microbial infection. The control group was matched according to the age of the case group (±3 years old) and the gestational age (±2 weeks) to exclude adverse pregnancy outcomes such as stillbirth, congenital malformation, premature delivery and low birth weight infants. A total of 192 subjects were included. Questionnaires were used to collect information of all subjects, and 12 ml of peripheral venous blood was collected to detect blood arsenic levels. Blood arsenic levels were divided into low concentration group (<1.00 μg/L), medium concentration group (1.00-1.50 μg/L) and high concentration group (>1.50 μg/L). The multivariate conditional logistic regression was performed to analyze the relationship between blood arsenic exposure and URSA and explore the influencing factors of blood Arsenic. Results: The geometric mean values of blood arsenic level in the cases group and control group were 1.68 (1.50-1.86) μg/L and 1.26 (1.17-1.37) μg/L, respectively. The blood arsenic level in the case group was significantly higher than that in the control group ( P< 0.05). The results of multivariate conditional logistic regression analysis showed that after adjusting for tobacco exposure during pregnancy, pre-pregnancy body mass index and the effects of residential decoration in past five years, the risk of URSA was higher in the high-concentration group compared with the low-concentration group ( OR =2.56, 95 %CI :1.06-6.24). Conclusion: Blood arsenic may increase the risk of URSA in women of childbearing age.

Chronic fluoride-arsenic combined poisoning is a global public health problem. While the cause of the disease is clear, the pathogenesis is unknown. Given that there is no specific treatment, early prevention is particularly important. Biological exposure limits are designed to investigate the maximum allowable concentration of harmful effects from exogenous chemicals. To explore the biological exposure limits for mixed exposures of fluoride and arsenic, we compared the contents of fluorine and arsenic in the environmental media of the control and fluoride-arsenic combined exposure areas and analyzed the dose-effect and dose-response relationship between fluoride, arsenic and the key proteins of Wnt signaling pathways. The benchmark dose method was used to estimate the biological exposure limit for fluoride-arsenic combined exposure. The results showed that the content of fluoride in coal, clay, indoor air, outdoor air, chili and rice, as well as arsenic content in coal, clay, outdoor air, chili and rice was higher than that of the control. With the increase of fluoride and arsenic exposure levels, the glycogen synthase kinase 3&beta; (GSK3&beta;), &beta;-catenincontents and the prevalence of Wnt/&beta;-catenin signaling pathway antagonistic protein Dickkopf-1 (DKK1), GSK3&beta;, Beta-catenin (&beta;-catenin) gradually increased, but the content of DKK1 significantly decreased. Based on the Wnt signaling pathway, the biological exposure limit for fluoride-arsenic combined exposure was urinary fluoride of 0.52 mg&middot;g -1 creatinine and urinary arsenic of 6.59 mg&middot;g -1 creatinine. Our results had important guiding significance for early prevention of body damage caused by fluoride-arsenic combined poisoning.

Objective: To explore the changes and influencing factors about expressions of tumor-related gene mRNA in workers who smelt arsenic., Methods: There were 37 workers who smelt arsenic, 43 workers who stopped exposure to arsenic for 85 days, and 51 individuals as control group which selected by random cluster sampling. Arsenic species( iAs, MMA, and DMA) in urine were determined by atomic absorption spectrophotometer with an As speciation pretreatment system. Real time PCR( RT-PCR)was performed to detect the expressions of 4 tumor-related gene mRNAs., Results: The concentrations of iAs, MMA and DMA in urine of workers who smelt arsenic, stopped exposure to arsenic for 85 days, and control group were( 133. 97 ± 109. 53), ( 208. 93 ±171. 43) and( 820. 35 ± 487. 39) μg/( g·creatinine)( workers who smelt arsenic), ( 123. 31 ± 112. 72), ( 176. 21 ± 157. 19) and( 467. 73 ± 392. 17) μg/( g·creatinine)( workers who stopped exposure to arsenic), ( 1. 55 ±1. 49), ( 0. 10 ±0. 09) and( 10. 47 ±7. 85) μg/( g·creatinine)( control group). Compared to control group, the concentrations of 3 arsenic species were all higher in worker came from arsenic smelting. Compared to workers who were smelting arsenic, DMA are lower in workers who stopped exposure to arsenic for 85 days( P < 0. 05). The relative mRNA expressions of Lin28, Bax, Bcl-2 and Fas in 3 groups were( 8. 88 ± 2. 42), ( 6. 87 ± 1. 10), ( 7. 24 ± 2. 31) and( 8. 23 ±2. 90)( workers who smelt arsenic), ( 6. 21 ± 2. 94), ( 5. 81 ± 1. 72), ( 4. 50 ± 1. 59)and( 6. 89 ± 2. 35)( workers who stopped exposure to arsenic), ( 5. 60 ± 1. 43), ( 5. 56 ±0. 98), ( 4. 88 ± 1. 39) and( 6. 92 ± 1. 87)( control group). Compared to control group, relative mRNA expressions of Lin28, Bax, Bcl-2 and Fas were all higher in worker who were smelting arsenic( P < 0. 05)., Conclusion: The expressions of tumor-related gene mRNAs are high in workers who smelt arsenic, and the methylation metabolism of arsenic play great role in the process of relative mRNAs expresses.

Objective: To detect the chemical pollutants concentrations of dietary salt and to comprehend the effect of chemical pollutants on the quality of salt., Methods: 45 kinds of salt with different countries, brands and types were collected in Shanghai during May to June in 2015. Five different heavy metal elements, fluoride, potassium ferrocyanide and 16 phthalate plasticizers were measured, and the result were analyzed with the standard., Results: The salt of largest consumption was domestic halite/well salt in Shanghai, accounting for 87. 6% of the total salt consumption. Lead was detected in only two types of salt at concentrations recorded of 0. 047 and 0. 077 mg/kg, which were far below the Chinese national standard. The concentrations of total arsenic, total mercury, cadmium, and barium were lower than the limit of detection( LOD) in all samples. The median fluoride concentration of salts was 0. 16 mg/kg( maximum 2. 50 mg/kg). The median fluoride concentration of domestic salts was significantly lower than foreign-produced salts( P < 0. 05), and it was significantly higher in sea salt than in other types of salt. The median potassium ferrocyanide concentration in 12 types of salts was4. 30 mg/kg( maximum 9. 2 mg/kg), which was lower than the Chinese national standard. Just 3 salt types had low levels of bis( 2-ethylhexyl) phthalate concentrations that were above the LOD, at 0. 208, 0. 375 and 0. 380 mg/kg, respectively., Conclusion: The level of chemical pollutants in salt is either very low or absent.

Objective: To determine the effects of arsenic and estrogen receptor antagonist (ICI182, 780) on the expression of estrogen receptor beta (ERβ) in alveolar Ⅱ epithelial cells (AECⅡ) of female and male mice., Methods: Nineteen or twenty day fetus mice were obtained through caesarean section of ICR mice. Purified AECⅡ cells were separated from the female and male fetus,respectively,and confirmed using immunofluorescence staining. The cells were exposed to sodium arsenite (NaAsO 2 ) at a low,medium,or high dosage determined by MTT and cultured for 24 h. The NaAsO 2 (5 μmol/L) exposed cells were compared with those treated (for 24 h) with dimethyl sulfoxide (DMSO) or ICI182, 780 (1×10 -4 mol/L). Apoptosis rates of the cells were measured by flow cytometry. Real-time fluorescence quantitative PCR method and Western blot technique were used to detect the expression of ERβ mRNA and protein in AECⅡ., Results: Purity of AECⅡ cells reached (87.0±2.5)%. NaAsO 2 exposure was set at a concentration of 0.5 (low),1.25 (medium),and 5 (high) μmol/L. The cells exposed to medium and high dosage of NaAsO 2 had higher apoptosis rates than the blank controls ( P <0.05),without sex differences. Female cells exposed to medium and high dosage of NaAsO 2 had higher levels of expressions of ERβ mRNA and protein than the blank controls ( P <0.05) and male cells exposed to the same dosage of NaAsO 2 ( P <0.05). No significant differences were found in the expressions of ERβ mRNA and protein between the exposed male cells and the blank controls. ICI182, 780 lowered the expression levels of ERβ mRNA and protein in the female exposed cells ( P <0.01)., Conclusion: Arsenic exposure increases expressions of AECⅡ's ERβ,more so in female cells than in male cells. This can be blocked by estrogen receptor antagonists., (Copyright© by Editorial Board of Journal of Sichuan University (Medical Science Edition).)

Objective: To understand the daily intake of arsenic via daily dietary of Shaanxi inhabitants, and to assess the possible adverse health impact., Methods: The arsenic contents of 4287 samples were analyzed statistically. The safety of arsenic intake was evaluated by using the dietary arsenic PTWI recommended by JECFA. The health risk was assessed with USEPA health risk assessment model., Results: The arsenic contents of grains and vegetables were 0. 0265 mg / kg and 0. 0271 mg / kg, respectively. Grains and vegetables were major part of the daily diet of residents, 80% of dietary arsenic intake was from which. The average and the higher dietary intake of arsenic were 0. 423 and 1. 10μg /( kg·d), respectively, which was lower than the standard of PTWI recommended by JECFA. But the values of the individual health risk were 9. 03 × 10~(-5) and 2. 34 × 10~(-4)a~(-1), the both of which were higher than the standard of ICRP. That showed a potential health risk from As via dietary exposure for the residents., Conclusion: Although the average dietary intake of arsenic is in a safe range, the health risk caused by the risk cannot be ignored.

Objective: To study the effect on endocrine system of SD rats exposed to low-dose arsenic., Methods: A subchronic test on rats which were divided into five groups randomly( the control group, 0. 05, 0. 1, 0. 2, 0. 4 μg / m L), 20 rats each group, half male and female. A total of 200 rats were allowed to acclimate for 1 week and their hormones level were measured by RIA method after 110 and 194 days., Results: The hormones level of rats was disordered in different groups. The T level of male rats exposedto arsenic for 110 days were( 4. 80 ± 4. 26), ( 4. 54 ± 3. 31), ( 1. 27 ± 1. 51), ( 1. 93 ±2. 23) and( 4. 83 ± 2. 31) ng / m L( P = 0. 05), respectively. The T4 level of each female group were( 40. 20 ± 7. 10), ( 40. 85 ± 8. 66), ( 46. 49 ± 8. 52), ( 44. 66 ± 11. 83) and( 26. 80 ± 8. 12) ng /m L, compared with control group, 0. 4 μg /m L group decreased obviously( P < 0. 05). Meanwhile, their Cort level of each group were( 312. 10 ±10. 61), ( 333. 15 ± 15. 73), ( 341. 13 ± 19. 25), ( 342. 59 ± 25. 96) and( 314. 84 ±16. 76) ng / m L, and the 0. 05, 0. 1 and 0. 2 μg / m L groups were significantly increased( P < 0. 05). Furthermore, the T4 level of male groups exposed to arsenic for 194 days were( 23. 06 ± 5. 54), ( 33. 18 ± 5. 29), ( 34. 23 ± 4. 15), ( 37. 19 ± 4. 13) and( 39. 92± 6. 27) ng / m L, respectively. Compared with control group, all experimental group significantly increased( all P < 0. 05). Additionally, the T3 level of female group were( 0. 84 ± 0. 12), ( 0. 89 ± 0. 14), ( 0. 83 ± 0. 15), ( 0. 96 ± 0. 16) and( 0. 75 ± 0. 11)ng / m L, and 0. 2 μg / m L group obviously increased( P < 0. 05). Obvious change of hormone had not been found in other group exposed to subchronic low-dose arsenic( all P> 0. 05)., Conclusion: Subchronic low-dose arsenic exposure have slight endocrine effects on SD rats.

Objective: To observe the effect of chronic arsenic exposure on cerebral cortex and serum metabolics of mice and explore the mechanism of arsenic neurotoxicity., Methods: Twelve 3-week-old male C57BL/6J mice were randomly assigned into exposure group and control group and exposed to sodium arsenite (50 mg/L) via drinking water and deionized water for 12 weeks, respectively. After the exposure, arsenic level in the cerebrum was determined by hydride generation-atomic fluorescence spectrometry. The metabolites in the cerebral cortex and serum were determined using gas chromatography-mass spectrometry (GC/MS) analysis. Principal component analysis (PCA) was used to analyze the difference of the metabolites between the exposure and the control groups. Online tools for analyzing metabolic pathways were used to identify the related metabolites pathways., Results: Arsenic content in the brain of exposure group was significantly higher than that in the control group (P<0.05). The mice exposed to arsenic had a higher level of citric acid, phenylalanine, tyrosine, histidine and lysine in the cerebral cortex (P<0.05). Serum levels of serine, glycine, proline, aspartate and glutamate were significantly higher while α-ketoglutaric acid level was significantly lower in the exposure group than in the control group (P<0.05). PCA analysis showed a significant difference in cerebral cortex and serum metabolites between the two groups., Conclusion: Chronic arsenic exposure may affect the function of the central nervous system by interfering with amino acid metabolism and tricarboxylic acid cycle, which may be one of the mechanisms of arsenic neurotoxicity.

Objective: To evaluate five heavy metal biotoxicity effects on Caenorhabditis elegans with Meta regression analysis., Methods: The data were collected from the following electronic databases：PubMed, Web of Science, EBSCO, the Chinese Biomedical Database, Chinese National Knowledge Infrastructure, Wan Fang (Chinese) Databases and so on, and all updated through January 2004 to December 2014. A literature review was made on articles about Cd, Hg, Pb, As and Cr toxicity effects on C. elegans , and the data was extracted from figure information by Scan It software. A Meta regression model was built by stata12.0 software, using toxicity indices such as the dependent variables, and different metals, concentrations, exposure time, and development stages of C. elegans as independent variables., Results: The study articles asociated with heavy metal biotoxicity effects on C. elegans were selected out, 10 studies of Cu, 12 studies of Cr, 12 studies of Pb, 12 studies of Cd, 3 studies of As and 14 studies of Hg. The mortality of toxicities of 5 heavy metals on C. elegans ranked Hg > Pb > Cr> Cd>As; the biotoxicity of the indexes of body size based on development, generational time based on reproductive toxicity, body bend frequencies, and head thrash frequencies based on neurotoxicity ranked Hg > Pb > Cr > Cd; the biotoxicity ranked Hg > Pb > Cr> Cd>As by LC 50 indexes of toxicities of 5 heavy metals on C. elegans . The sensitivity analysis proved that the Meta regression model was reliable., Conclusions: The biotoxicities on C. elegans of Hg and Pb are stronger than Cr, Cd and As.

Objective: To explore the intervention effects of lutein on liver toxicity in mice induced by arsenic trioxide (As2O3) and to evaluate the preventive effect and the antioxidant mechanism of lutein., Methods: A total of 84 healthy KM mice were randomly divided into eight groups. There were 35 d control group, 70 d control group, 35 d lutein group, 70 d lutein group, arsenic exposure group, lutein treatment group and lutein prevention group. The activity and level of AST, ALT, T-AOC, MDA, GSH, SOD, NO in liver tissue were measured by kits. Compares the difference between each group of the single factor analysis of variance., Results: The activity of ALT, AST and the contents of MDA of 70 d control group were significantly lower than that arsenic exposure group. The contents of GSH, T-AOC, NO and the activity of SOD of 70 d control group were increased significantly than arsenic exposure group. The activity of ALT, AST and the contents of MDA of lutein prevention group were significantly lower than that lutein treatment group. The contents of GSH, T-AOC, NO and the activity of SOD of lutein prevention group were increased significantly than lutein treatment group. The differences were statistically significant (P < 0.05)., Conclusion: Lutein can improve antioxidation function and has protective effect on liver injury of mice induced by arsenic.

Objective: To observe theexpression variations of estrogen receptor alpha (ERalpha) in different periods of mice offspring and the gender-dependent differences in the lung tissue with parental arsenic exposure., Methods: Parental female mice were exposed to arsenic by gavage from gestational day 8th to offspring infancy, and offspring were exposed to arsenic by drinking water after infancy. The expression level of ERalpha mRNA and protein in lung tissue of the male and female offspring in different developmental periods and different doses (low, middle, high) of sodium arsenite exposure were detected by real-time PCR and Western blot., Results: ERalpha mRNA expression in female lung tissue was lower than male in embryonic period (P<0.05); ERalpha mRNA expression in female lung tissue was higher than that of male in infant and adult periods (middle dose of infancy P<0.05, middle and high doses of adulthood P<0.05); No statistical significances were observed in embryo, infancy and adulthood control groups. ERalpha mRNA expression in female lung tissue of infancy and adulthood was higher than that in embryonic period (low, middle and high dose groups P<0.05). ERa protein expression in arsenic exposed female lung tissue was higher than that of male in infant and adult periods, it was also increased by compared with corresponding control groups (P<0.05). The expression level of ERalpha protein in exposed adult female and male offspring were higher than that of infancy., Conclusion: Arsenic infected during pregnancy can increase the lung tissue's ERalpha expression level of female offspring in infancy and adulthood. This result is significant to elucidate the role of environment pollutants in gender difference of lung cancer's occurrence.

Objective: To detect ERbeta mRNA expression of subjects exposed to different arsenic drinking water, and to analyze the potential relationship between their abnormal expression and heart injury caused by arsenic in order to study the endocrine disturbing effect of arsenic., Methods: Molecular epidemiological method was used. The study subjects included a total of 273 residents exposed to arsenic via drinking water,and they were divided into four groups according to arsenic concentration, and their blood ERbeta mRNA expression was detected by real-time RT-PCR., Results: The level of ERbeta mRNA expression rose with increasing of water As and urine As (r = 0.159, 0.21, P < 0.05). The prevalence of Q-Tc interval prolongation aggravated with increasing of water As(chi2 = 4.35, P = 0.037), while according with the variation of ERbeta mRNA expression. Tp-Te interval prolonged with increasing of water As (r = 0.199, P = 0.023), as well prolonged with increasing of ERbeta mRNA expression (r = 0.205, P = 0.019). The prevalence of arrhythmia was almost according with the variation of ERbeta mRNA expression., Conclusion: chronic arsenic exposure can potentially disturb ERbeta mRNA expression, as well as there are possible relationship between ERbeta mRNA abnormal expression and Q-Tc interval prolongation and Tp-Te interval prolonged caused by arsenic.

Thesis aims at evaluating and setting priority to human toxicity and ecotoxicity of coking pollutants. A field research and sampling project are conducted in coke plant in Shanxi so as to complete the coke emission inventory. The USEtox model representing recommended practice in LCIA characterization is applied to the emission inventory to quantify the potential impacts on human toxicity and ecotoxicity of emerging pollutants. Priority pollutants, production procedures and effects of changing plant site on the toxicity are analyzed. As conclusions, benzo(a) pyrene, benzene, Zn and As are identified as the priority pollutants in human toxicity, while pyrene and anthracene in ecotoxicity. Coal charging is the dominant procedure for organic toxicity and priority pollutants include benzo (a) pyrene, benzene, naphthalene, etc. While coke drenching is the dominant procedure for metal toxicity and priority pollutants include Zn, As, Ti, Hg etc. Emission to rural environment can reduce the organic toxicity significantly compared to the emission to urban environment. However, the site changing has no effect on metal toxicity and might increase the risk of the metal pollution to rural water and soil.

Objective: To study the arsenic distribution, speciation, its effects on the balance of other elements and the DNA damage by subchronic arsenite exposure in mice., Methods: The 8-week-old C57BL/6N mice were matched by weight and divided into control group and supplementation group, which were given 0 or 10 microg/ml of sodium arsenite in the drinking water, and continuous exposed for 6 months., Results: Arsenic was found in various tissues and organs. The highest ones were in the kidney, lung and liver, reached (563.9 +/- 222.5), (458.6 +/- 191.0) and (279.8 +/- 81.2) ng/g, respectively while the lowest in the blood and brain, reached (82.2 +/- 26.7) ng/ml and (101.8 +/- 30.1) ng/g, respectively. Arsenic exists mainly in the form of dimethylarsinous acid (DMA). Compared to the control group, there was a significant difference (P < 0.05) between arsenic and chromium, copper, zinc, selenium, lead in some organs of arsenic exposed group, but not cadmium. Furthermore, the 8-hydroxydeoxyguanosine (8-OHdG) level of the exposed group was (149.1 +/- 1.0) ng/ml, which was significantly higher than the control group of (76.4 +/- 27.9) ng/ml., Conclusion: Arsenic accumulated in various tissues and organs mainly in the form of DMA, which affected the balance of chromium, copper, zinc, selenium and lead in the body, and led to DNA damage after subchronic exposure.

Objective: To observe the mRNA expression of nerve growth factor (NGF) and nerve growth related proteins-43 (GAP-43) on hippocampus of F1 generation female rats after the pregnancy and lactation rats exposure to arsenic sodium., Methods: 12 of pregnancy rats were exposed to arsenic (0, 10, 50, 100 mg/L, respectively in drinking water) from the 6 gestation day till F1 pups being 21 days old. Select females for expriments. Observe the change of form and numbers in CA1, CA3, DG area neurons in hippocampus by HE and Nissl's stain. By means of reverse transcription polymerase chain reaction (RT-PCR), NGF and GAP-43 mRNA in hippocampus tissues in rats was measured., Results: HE stain showed that, in CA1 and CA3 area, the structure of hippocampus neurons was normal in control group. In experiment groups, the apoptosis phenomena were found in hippocampus neurons including edge unclear, cell shrinkage and nuclear condensation, especially in high dose group. The hippocampus neuronal cytoplasm was rich in Nissl bodies in control group with Nissl's stain. With the experiment dose increasing, Nissl bodies were decreased especially in CA1 area. RT-PCR results demonstrated that the expression of NGF and GAP-43 mRNA were reduced significantly in experiment groups when compared with that of control (both P < 0.01). The expression of NGF and GAP-43 mRNA were decreased as the dose of arsenic increasing (both P < 0.05)., Conclusion: Rats exposure to arsenic during pregnancy and lactation, can damage hippocampus neuronal cell, and restrain the NGF and GAP-43 mRNA expression of F1 generation female rat, damaged the learning and memory ability at last.

Objective: To study the effect of realgar on Glu and Gln on rat brain tissues., Methods: Forty-eight Wistar rats were divided into 4 groups randomly:control group,low dosage group, moderate dosage group and high dosage group. The treatment groups were treated with realgar by gastric perfusion at a dosage of 0.3 g/kg, 0.9 g/kg, 2.7 g/kg and the control group ones were orally given the same volume of 0.5% sodium carboxymethylcellulose (CMC-Na) for 6 weeks. The contents of inorganic arsenic, monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA) in brain tissues were measured by hydride generation-atomic absorption (HG-AAS) method. The contents of amino acid neurotransmitters in brain tissues of rats were determined by means of high performance liquid chromatography with precolumn derivatization., Results: The levels of MMA and DMA in brain increased as the dosage of realgar increased, while the second methylation index declined. Compared with control group,the levels of Glu was significantly decreased in realgar treated group (P < 0.05); Gln also tended to decrease and that of low dosage group was obviously decreased compared with controls., Conclusion: Realgar exposure can cause accumulation of MMA and DMA,declination of second methylation index and the reduction of Glu and Gln in brain tissue.

It was an urgent problem to determine short-term exposure safety concentration of genetic carcinogens in water pollution accident in China. Based on the hypothesis that the relationship between exposure dosage and carcinogenic risk was linear, the calculation process of genetic carcinogens safety concentration was put forwarded, and the method using life-time exposed safety concentration to calculate short-term exposure safety concentration was set up. Based on the statistical result of water pollution accident occurred in china during 2000-2010, arsenic was a major characteristic contaminate in water pollution accident. According to the method of short-term exposure safety concentration of genotoxic carcinogens, the safety concentration of arsenic was 0.5 mg x L(-1), it showed that the method was feasible in emergence management of water pollution accident.

Badu Shengji San(BDSJS) is a traditional Chinese medicine (TCM) used for drawing out toxin, eliminating suppuration and promoting granulation. Toxic minerals such as arsenic and lead are the two most important components of BDSJS. Previous hypothesis indicated that according to the compatibility theory of TCM, the toxicity of the entire BDSJS was weaker than that of arsenic and lead, respectively. In the present study, SD rats with injured skin were treated with distilled water and different composition of BDSJS (complete formulations, compatible herbs, mineral medicine containing arsenic and lead, mineral medicine containing arsenic and mineral medicine containing lead) once a day for consecutive 2 weeks. Kidney coefficient and urinary beta-N-acetyl glucosidase (NAG) were used as the indicators of renal toxicity and the content of malondiadehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), glutathione (GSH) and metallothionein (MT) in the renal tissue were measured. Our data showed that kidney coefficient, the severity of renal pathological lesion and MT level in the kidney of the entire BDSJS group decreased significantly compared with arsenic and lead group. Additionally, the NAG content of the entire BDSJS group had the decreased trend. The kidney CuZn-SOD level of the entire BDSJS group had the increased trend, but the MDA, GSH-PX, GSH level had no obvious difference. Our results suggested that compatible herbs in BDSJS relieved renal injury induced by arsenic and lead, and the attenuation mechanism may be related to MT and CuZn-SOD, but not to MDA, GSH-PX and GSH directly.

Objective: To explore arsenic accumulation and toxicity mechanism following long-term use of realgar and provide scientific basis for safety use of realgar in clinic., Method: The realgar which was used in the study contains 90% insoluble asenic sulfide (As2S2) and 1.696 mg x kg(-1) soluble arsenic. Two separate experiments were performed: 1) Twenty-eight fasting SD rats were orally given a single dose of realgar at the dose of 0.8 g x kg(-1) and the other four rats were given ultra-filtrated water served as control group. Blood, hearts, livers, kidneys, lungs and brains of four rats were taken out at 0.5, 1, 2, 4, 8, 16, 36 h respectively after treatment. Asenic quantity of each organ or blood sample was measured. 2) Forty SD rats were randomly divided into four groups: control group and realgar 0.02, 0.08, 0.16 g x kg(-1) groups, each group containing 5 females and 5 males. The rats were intra-gastrically treated with realgar once a day for successively 90 days, while the control group was given ultra-filtrated water. Asenic amount in blood, liver, kidney and brain of each rat was measured in fasting rats at 16 h after last dosing., Result: Asenic amount of blood, liver, kidney, heart, lung and brain increased after single dosing of realgar at dose of 0.16 g x kg(-1), with the order from high to low blood > kidney > lung > liver > heart > brain. Asenic amount was much higher in blood than that in other organs. The feature of asenic distribution in blood following realgar administration may be the basis for its use for leukemia Ninety-day oral treatment of realgar led to significant accumulation of asenic in blood, kidney, liver and brain. The highest asenic accumulation times was found in kidney followed by liver, which was assumed to be associated with nephrotoxicity and hepatotoxicity of realgar. The highest amount of asenic was observed in blood after 90 day's administration of realgar, and the amount of asenic in organs was in the order of blood > kidney > liver > brain., Conclusion: Asenic can be absorbed and extensively distributed in various organs or tissesses after realgar administration in rats. Long-term use of realgar caused high asenic accumulation in various tissueses, including blood, kidney, liver, and brain. The nephrotoxicity and hepatotoxicity of realgar could be associated with the asenic accumulation in relative organs. Blood is the target of the most highest distribution and accamulation of asenic after realgar treatment, that could be associated with the efficacy of realgar on the treatment of leakemia.

Objective: To study the effects of inorganic arsenic on mRNA expression of transcription factor Nrf2 and Nrf2-regulated downstream anti-oxidant enzymes, NADPH: quinine oxidoreductase 1 (NQO1) and heme oxygenase 1(HO-1) in Chang hepatocytes., Methods: Chang hepatocytes were treated with 5, 10, 25 and 50 micromol/L of sodium arsenite (NaAsO2) for 6h, and RT-PCR were then performed to detect the mRNA expression of Nrf2, NQO1 and HO-1., Results: When exposed to 5, 10, 25 and 50 micromol/L of NaAsO2, Nrf2 mRNA were (100.74 +/- 3.70)%, (105.96 +/- 1.75)%, (101.76 +/- 1.01)% and (101.81 +/- 6.33)% of control,showing no statistic significance (P > 0.05). NQO1 mRNA expression were significantly increased (P < 0.05), and the levels of NQO1 mRNA were (106.52 +/- 3.11)%, (113.27 +/- 2.84)%, (111.96 +/- 6.96)% and (107.33 +/- 2.76)% of control, respectively. Moreover, HO-1 mRNA expression were also significantly induced by sodium arsenite exposure, and a definite dose-effect relationship was confirmed (P < 0.01)., Conclusion: No elevation of Nrf2 transcription was found, while inorganic arsenic could increase the Nrf2-regulated NQO1 and HO-1 mRNA expression in human hepatocytes.

Objective: To study the effect on endocrine system of female rats exposed to chronic arsenic., Methods: 50 female Wistar rats were randomly divided into five groups: control group, 0.05, 0.1, 0.2 and 0.4 microg/ml arsenic groups. The hormone levels were determined by RIA exposing arsenic for 32 weeks., Results: The hormone levels of female rats were disorder in different arsenic groups. E2, P level increased and LH level decreased in arsenic groups compared to controls, but there were no significant differences( P > 0.05). FSH and PRL level increased in low arsenic group and decreased in high arsenic groups (P > 0.05). GnRH and Cort level increased in arsenic groups, and GnRH level obviously increased in 0.4 microg/ml group and Cort level obviously increased in 0.1 and 0.4 microg/ml groups (P < 0.05)., Conclusions: The hormone levels were disordered in rats exposed to chronic arsenic.

Objective: To analyze speciation and toxicity of arsenic in realgar bioleaching solution, and to explore its possible relation between speciation and toxicity., Methods: Capillary zone electrophoresis (CZE) can be used quickly and simply onto the simultaneous separation and quantitative determination of the speciation of arsenic in realgar bioleaching solution. The effects of three different realgar bioleaching liquids on the acute toxicity level of rat were also investigated as well. Parallel experiments with traditional processing realgar via gastric irrigation were conducted for comparison., Results: There are three different arsenic species in realgar bioleaching solution (iAs(III), iAs(V) MMA(V)), and the processing method largely affected speciation and toxicity of arsenic of it. It was found that the toxicity level was decreased through increasing the amount of MMA(V)., Conclusion: These results indicate that the species of arsenic may be tightly relationship to its toxicity in realgar bioleaching solution.

Inorganic arsenic is one of proven human carcinogens, which there are so far no sound laboratory-based evidences and there are very few reports in the literature regarding arsenic carcinogenic effects in in vivo animal experiment. Because of this lack of adequate evidences, the mechanism for understanding arsenic toxicology remains vague. Recently, many modes of action for arsenic carcinogenesis have been proposed, oxidative stress is one of the stronger theories of arsenic action modes which have a substantial mass of supporting data. Further more, many researchers have pointed out that induction of oxidative stress by methylated metabolites of inorganic arsenics plays an important role in the toxicity and carcinogenicity of arsenics. The role of oxidative stress induced by arsenic in arsenic toxicology was reviewed.

Objective: To observe the effects of arsenic exposure through drinking water on methylation in persons., Methods: The levels of inorganic arsenic (iAs), monomethylated arsenic (MMA), dimethylated arsenic (DMA) in blood and urine were detected by atomic absorption spectrophotometer with an arsenic speciation pretreatment system. Total arsenic (tAs), the first methylation index (PMI) and the second methylation index (SMI) were calculated as iAs+ MMA + DMA, (MMA+ DMA)/tAs and DMA/(MMA + DMA), respectively., Results: iAs, MMA, DMA, tAs and PMI in blood of exposed persons were more higher than those of control, while SMI was more lower than that of control. Significant positive correlations were found between urinary MMA and blood PMI (r = 0.419, P < 0.01), while significant negative correlations were found between urinary MMA and blood SMI (r = -0.326, P < 0.05). No significant differences were found in methylation capacity between men and women., Conclusion: The arsenic methylation capacity of the persons exposed to arsenic was different from that of person non-exposed to arsenic, indicating an increase of PMI and decrease of SMI. There were no differences between sex in methylation capacity.

Objective: To study alone and combined effect of selenium and arsenic on oxidative stress, DNA oxidative damage and repair., Methods: HepG2 cells were treated with selenium (2.5, 5.0 and 10.0 micromol/L sodium selenite) alone, arsenic (1.56, 3.13, 6.25, 12.5 and 25.0 micromol/L arsenious acid) alone and combined selenium plus arsenic. The quantitative analysis of malondialdehyde (MDA), 8-OHdG and hOGG1 was carried out by fluorometric method, HPLC-EC and Western Blot to represent oxidative stress, DNA oxidative damage and repair, respectively., Results: Under the condition of alone treatment, sodium selenite (5.0 and 10.0 micromol/L) as well as arsenious acid (6.25, 12.5 and 25.0 micromol/L) resulted in significant increased levels of MDA and 8-OHdG, and inhibition of hOGG1 expression in HepG2 cells compared with solvent control (P < 0.05, P < 0.01). Sodium selenite at the relative low dose (2.5 micromol/L) displayed certain anti-oxidative ability (P > 0.05). Combined treatment of sodium selenite (2.5 micromol/L) and arsenious acid (6.25 micromol/L) caused significant lower levels of MDA and 8-OHdG than those of correspondent arsenic alone treatment (P < 0.05). hOGG1 expression showed no difference between combined treatment (2.5 micromol/L of selenium selenite plus 6.25, 12.5 and 25.0 micromol/L of arsenious acid, respectively) and correspondent arsenic alone treatment (P > 0.05)., Conclusion: Sodium selenite at the concentrations of 5.0, 10.0 micromol/L and arsenious acid at the concentrations of 6.25, 12.5, 25.0 micromol/L induced enhanced oxidative stress and 8-OHdG production, and inhibition of hOGG1 expression, respectively. Selenium at certain concentration (2.5 micromol/L of selenium selenite) has ameliorative effects on oxidative stress and DNA oxidative damage induced by arsenic, but no effect on repair of DNA oxidative damage.

Objective: To explore the effect of glutathione and L-methionine on the distribution and methylic metabolism of arsenic speciation in the liver, blood and kidney of mice exposed to inorganic As through drinking water., Methods: Mice were randomly divided into control groups (Con), the only groups with arsenic (As group), GSH intervention groups (GSH) and L-Met intervention groups (L-Met). The mice of experimental groups were exposed to arsenite by drinking water at the concentration of 50 mg/L arsenite for 4 weeks. The GSH groups and the L-methionine groups were injected with glutathinone and L-methionine respectively on the fifth week. Livers, bloods and kidneys were taken to determinate the concentrations of inorganic (iAs), monomethylarsenic acid (MMA) and dimethylarsenic acid (DMA) using hydride generation trapping by ultra-hypothermia coupled with atomic absorption spectrometry., Results: In liver, contents of DMA in L-methionine groups were moer higher than those of the As group. The primary methylic indexes (PMI) of arsenic speciation in the GSH groups and the secondary methylic indexes (SMI) of arsenic speciation in the GSH groups and L-methionine groups were more higher than those of the As group. In blood, contents of DMA and the total arsenic speciation (TAs) in both GSH groups and L-methionine groups were more higher than those of the As group. The PMI of arsenic speciation in both GSH groups and L-methionine groups were more higher than those of the As group., Conclusion: GSH and L-methionine could promote the methyee metabolism of iAs. As a result, the content of DMA, the end product of methylated metabolism of arsenic, rises, which facilitates the methylic metabolism and excretion of iAs.

Objective: To investigate the relationship between genetic polymorphisms of GSTT1, GSTM1 and arsenic methylation level., Methods: 247 residents in an industrial arsenic polluted village were randomly selected as subjects. The genetic polymorphisms of GSTM1 and GSTT1 were detected by multiple PCR method. Urinary inorganic arsenic (iAs), monomethylarsenic acid (MMA) and dimethylarsenic acid (DMA) concentrations were determined by ion chromatogram combined with HG-AFS., Results: No significant differences in the relative proportion of urinary iAs, MMA and DMA were observed between the individuals with GSTT1 positive genotype and the individuals with GSTT1 null genotype. No significant differences in the relative proportion of urinary iAs, MMA and DMA were observed between the individuals with GSTM1 positive genotype and the individuals with GSTM1 null genotype. And no significant differences in the relative proportion of urinary iAs, MMA and DMA was observed among the individuals with different GSTM1 and GSTT1 associated genotype., Conclusion: The polymorphisms of GSTT1 and GSTM1 were not associated with arsenic metabolism level in the studied population.

A series of molecular environmental epidemiological studies have been carried out to elucidate biomarkers of exposure, effect, and susceptibility for arsenic-related health hazards in Taiwan area in China. Arsenic levels in urine, hair, and nail could be biomarkers for short-term internal dose, skin hyperpigmentation and palmoplantar hyperkeratosis could be biomarkers for long-term (many years) internal dose, and percentage of monomethylarsonic acid in total metabolites of inorganic arsenic in urine could be considered as an exposure marker for biologically effective dose. The biomarkers of early biological effects of ingested inorganic arsenic could include blood levels of reactive oxidants and antioxidant capacity, genetic expression of inflammatory molecules, as well as cytogenetic changes including sister chromatid exchange, micronuclei, and chromosome aberrations of peripheral lymphocytes. Biomarkers of susceptibility to arsenic-induced health hazards could include genetic polymorphisms of enzymes involved in xenobiotic metabolism, DNA repair, and oxidative stress, as well as serum level of carotenoids. Gene-gene and gene-environment interactions could be involved in arsenic-induced health hazards through toxicological mechanisms including genomic instability and oxidative stress.

Objective: To study the leaching toxicity of the ferric salt and aluminum salt containing arsenic-bearing sludge coming from the high arsenic drinking water treated by coagulation/microfiltration process and its disposal method., Methods: The Chinese standard method and TCLP method issued by USEPA were used to test the leaching toxicity of arsenic-bearing sludge and its Portland cement solidification tests were conducted. Minor ferric salt containing arsenic-bearing sludge was added into road-application concrete for its utilization., Results: The arsenic concentrations in TCLP leaching solutions of ferric salt and aluminum sludge were 118 microg/L and 420 microg/L, respectively, which were higher than 9.5 microg/L and 11.8 microg/L of the Chinese standard method. However, all of them were less than identification standard for hazardous wastes of China. When arsenic-bearing sludge was solidified with cement, its leaching toxicity reduced about 90%. The unconfined compression strengths of solidification products were 3.25MPa and 0.76MPa which could meet the requirement for the landfill and sludge reclamation. The compression strengths of road-application concrete were upgraded about 12% when minor parts of ferric salt arsenic-bearing sludge was added., Conclusion: Ferric salt and aluminum salt arsenic-bearing sludge do not belong to the hazardous waste with leaching toxicity. Cement solidification is an efficient method for the disposal of arsenic-bearing sludge. The mix of arsenic-bearing sludge with road-application concrete could provide a method for the efficient utilization of arsenic-bearing sludge. At the same time, the possible environmental problems should be avoided.

Objective: To evaluate the relationship between the metabolism of arsenic and the damage of exon 5 and 8 of p53 gene from workers in a arsenic mill, and with real-time PCR technique, to establish the method probing the gene-specific DNA damage in people., Methods: By real-time PCR, the damages of exon 5 and 8 of p53 gene were probed in 37 workers exposed highly to, 16 manager and logistic employees exposed less to an arsenic mill in Yunnan province, and also 25 local people who did not contact with any white arsenic in near past time. At the same time, the urinary total and organic arsenic of workers were detected. The correlation between metabolism of arsenic and damage of p53 gene was evaluated., Results: Total urinary arsenic concentrations were (1.18 +/- 0.76) mg/L and (0.32 +/- 0.28) mg/L for high and low exposed male workers, and 0.23 mg/L, (0.53 +/- 0. 30) mg/L for high and low exposed females. Organic urinary arsenic concentrations were (0.48 +/- 0.37) mg/L and (0.08 +/- 0.05) mg/L for high and low exposed males, and 0.11 mg/L, (0.30 +/- 0.24) mg/L for high and low exposed females. The total and organic urinary arsenic of high exposed group was higher than that of control male (P < 0.05), all in control group were lower than 0.02 mg/L for reference. The Ct relative value of exon 5 of p53 gene in high exposed group was higher than that in control male (P < 0.05), and the increased tendency of Ct relative value of exon 5 of p53 gene was found in workers with organic arsenic concentration going up (r(s) = 0.355, P = 0.011). The Ct relative value of exon 8 of p53 gene in low exposed group was higher than that in control male (P < 0.05), but the difference between high exposed and low exposed or reference's was not obvious (P > 0.05)., Conclusion: The damages in exon 5 and 8 of p53 gene in workers exposed to arsenic may be induced. The metabolism of arsenic may be very important in the damage of exon 5. It is feasible for real-time PCR technique used to detect gene-specific DNA damage in people.

Rorippa globosa has been identified as a new Cd-hyperaccumulating plant species. In the present study, growth responses of Rorippa globosa and its accumulation characteristics of Cd and As were examined under the condition of Cd-As combined pollution. The results showed that Cd and As had an antagonistic effect on enhancing the growth of the plants and Cd uptake and accumulation under the low concentration Cd and As treatments. When Cd and As concentrations were 10 mg/kg and 50 mg/kg, the highest height of the plants and the dry weight of shoots were up to 35.9 cm and 2.2 g/pot, respectively; and the accumulation of Cd in the leaves under the combined pollution was higher than that at the same level under single Cd pollution. However, there were synergic adverse effects on plant growth and Cd uptake under the high concentration Cd and As combined pollution. Meanwhile the accumulation of As in the roots was higher than that in the shoots, the translocation factor < or = 0.3 and the bioaccumulation factor < or = 0.6, which showed that Rorippa globosa had an excluding effect on As uptake. These results confirmed that Rorippa globosa had the strong tolerance ability to the Cd-As combined pollution, and the potential applied to phytoremediation of contaminated soil by Cd and As.

Objective: To study the changes of genotoxicities of workers occupationally exposed to arsenic in a mill of Yunnan Province., Methods: The micronucleated cell and micronucleus frequency, comet rate and tail length of lymphocyte in comet assay from peripheral blood, urinary total and organic arsenic were detected and evaluated in 40 workers (exposure group), and also local people who did not contact with any poison obviously (control group)., Results: The micronucleated cell and micronucleus frequencies, the comet rate and tail length of lymphocyte in exposure groups were all more higher than those of controls (P < 0.01). The urinary total and organic arsenic concentrations in exposure groups were more higher than those of controls (all lower than 0.02mg/L for controls). The increased tendencies of micronucleated cells and micronucleus frequencies with the products of organic arsenic concentrations and service length were found in exposure groups(r(s) = 0.356, P = 0.024, r(s) = 0.347, P = 0.028). CONCLUSION indicated that arsenic could induce the damage of chromosome and DNA in lymphocyte of peripheral blood in workers occupationally exposed to arsenic.

Objective: To investigate the difference of arsenic metabolism in populations with long-term high arsenic exposure and explore the relationship between arsenic metabolism diversity and skin lesion., Methods: 327 residents in an arsenic polluted village were voluntarily enrolled in this study. Questionnaire survey and medical examination were carried out to learn basic information and detect skin lesions. Urinary inorganic and methylated arsenic were speciated by high performance liquid chromatography combined with hydride-generation atomic fluorescence spectrometry. Total arsenic concentration in hair was determined with DDC-Ag method., Results: Hair arsenic content of studied polutions was generally high, but no significant difference were found among the studied four groups. MMA and DMA concentration in urine increased with studied polution age, and were positively related with skin lesion grade. The relative proportion of MMA in serious skin lesion group was significantly higher than in other 3 groups, while DMA/MMA ratio was significantly lower than control and mild group. The relative proportion of MMA was positively related with skin lesion grade, DMA/ MMA ratio was negatively related with skin lesion grade. Males could have higher arsenic cumulation and lower methylation capacity than those of females. The population of above 40 years old may have higher methylation capacity than those of adults below 40yeas old. Smokers and drinkers seemed lower methylation capacity than those of non-smokers and non-drinkers respectively., Conclusion: The methylation of arsenic could affect by several factors, including age gender, smoking and drinking. Arsenic methylation copacity mey be associated with skin lesion induced by arsenic exposure.

Objective: To explore risk factors of the patients with skin lesions from burning high-arsenic-contaminated coal in southern Shanxi Province., Methods: An epidemiological cross-sectional study was conducted in two villages of Hanbin District, Ankang City, Shanxi Province, where 198 participants were randomly selected. The parts of factors which were not significantly different were rejected via the single variable analysis and the collinear relationships were removed between the other factors using principal components analysis, and then the major risk factors of the skin lesions from burning high-arsenic-contaminated coal were obtained from stepwise logistic regression., Results: The single variable analysis showed that 11 influential variables were significantly associaed with coal-burning-arsenic-associated skin lesions, while principal component and logistic regression analysis showed that 6 variables could be the principal, which were period of burning arsenic-contaminating coal, ege, the arsenic content in blood, resident duration, the arsenic content in urine and hair, respectively., Conclusion: The results suggested that the major risk factors of the skin lesions related to burning coal-contaminating arsenic should be period of burning arsenic-contaminating coal, age, the arsenic content in blood, resident duration, the arsenic content in urine and hair.

Objective: To study the effect of high concentration arsenic in drinking water on children's intelligence., Methods: Pupils in Hangjinhou Qi were selected as subjects. Arsenic in drinking water and urine was determined. These subjects were divided into control( < 0.05mg/L, group A), mild exposure (0.05 - 0.1mg/L, group B) and heavy exposure group(> or = 0.1 mg/L, group C), according to arsenic concentration in drinking water. The Chinese combined Raven' s test was applied to evaluate the intelligence of children. In addition, the questionnaire survey was conducted to find out information, such as general information of households, source of drinking water, health of subjects and their parents, education of parents, etc., Results: The boys' average intelligence quotients (IQ) were 99.4 (group A), 96.5 (group B), 94.9 (group C). On the other hand, average IQs of girls were 101.3 (group A), 98.3 (group B) and 94.2 (group C) in the sequence from high to low. When other factors were adjusted, the average intelligence quotient of girls who exposured to arsenic higher than 0.1 mg/L were significantly decreased, compared with control groups, while boys' IQ did not show so., Conclusion: Children's ingested the dring water contaminating arsenic ( > 1.0mg/L) for the long run probably could have adverse effect on their intelligence development in some degree. Girls' IQ seemed more susceptible to arsenic.

Recent advances in our knowledge of arsenic carcinogenesis include the development of rat or mouse models for all human organs in which inorganic arsenic is known to cause cancer- skin, lung, urinary bladder, liver, and kidney. Tumors can be produced from either promotion of carcinogenesis protocols or from complete carcinogenesis protocols. Experiments with p53 + / - and K6/ODC transgenic mice administered dimethylarsinic acid (DMA) or arsenite have shown some degree of carcinogenic, cocarcinogenic, or promotional activity in skin or bladder. At present, with the possible exception of skin, the arsenic carcinogenesis models in wild-type animals are more highly developed than in transgenic mice. In this review, animal models of arsenic carcinogenesis are presented and discussed animal models of DMA carcinogenesis, transgenic animal models of arsenic carcinogenesis, and methylated metabolites of arsenic.

The study on the heavy metals-polluted soil of Qingshuitang District, Zhuzhou City showed that the main enriched heavy metals in the soil were Cd, Hg, As, Zn, Pb and Cu, among which, the former three had strong biotoxicity while the others had definite toxicity, with the average integrative pollution index being 6.40. The heavy metals enrichment in soil animals increased with increasing pollution degree. Especially for some species of Megascoiecidae, they had a high enrichment of Cd, with the enrichment index being 11.96. The species and quantity of soil animals decreased with increasing Cd concentration. Cd had an obvious biotoxic effect on Megsacoiecidae' s isozyme activity. The heavy metals enrichment in vegetables also increased with increasing pollution degree, but there existed obvious interspecies difference in Cd enrichment.

Objective: Effects of arsenic on the levels of estradiol (E2), follicle stimulating hormone (FSH), luteinizing hormone (LH) and prolactin (PRL) in serum of female rats, as well as histopathological changes of ovary and adrenal gland were researched., Methods: The hormone levels of female rats were determined by RIA exposing arsenic for 10 weeks, and histopathological examination of ovary and adrenal gland were performed with light microscope., Results: In spite of LH, there was no levels of three hormones (P > 0.05). However, different extents of histopathological changes in ovary and adrenal gland were found., Conclusion: LH is a sensitive index on hormones of female rats, but it may directly damage the reproductive system.