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Occupational Hexavalent Chromium Exposure Induced DNA Damgage And Its Genetic Susceptible Modification

Posted on:2012-03-04Degree:MasterType:Thesis
Country:ChinaCandidate:X ZhangFull Text:PDF
GTID:2154330332478910Subject:Epidemiology and Health Statistics
Abstract/Summary:PDF Full Text Request
Chromium (Cr) is one of the most important metal elements existing in the environment, which occurs predominantly in two valence states:trivalent chromium (Cr(Ⅲ)) and hexavalent chromium (Cr(Ⅵ)). Cr(Ⅲ) is involved in the metabolism of sugar and fat in human, and is the essential trace element. Cr(Ⅵ) is recognized as harmful element. Epidemiological studies have shown that exposure to Cr (Ⅵ) significantly increases the risk of respiratory tract cancer, and the incubation period can be more than 15 years. The lung cancer caused by occupational chromate manufacture industry was listed as one of occupational tumors by China in 1987. And Cr (Ⅵ) was classified as a human carcinogen (group 1) by the international Agency for the Research on Cancer (IARC) in 1990.Cr(Ⅵ) compounds can actively penetrate the cells membrane through channels to transfer isoelectric and isostructural anions such as SO42- and HPO42-channels. Cr(Ⅲ) compound, because of its poor membrane permeability, has been considered to have lower toxicity than Cr(Ⅵ). Cr(Ⅵ) is a strong oxidizing agent, and is reduced through short lived Cr intermediates (Cr(Ⅴ) and Cr(Ⅳ)) to the ultimate stable trivalent species (Cr(Ⅲ)). The reactions of Cr(Ⅵ) with biological reductants, such as ascorbate and thiols, might be accompanied by formation of organic radicals, which in turn cause O2 activation and formation of reactive oxygen species (ROS), and excessive quantities of ROS generated by these reactions would cause damage to cellular proteins and DNA leading to a state known as oxidative stress.Electroplating traditional electrolysis process is depositing chromium metal on the surface of steel, copper and alloys through electrochemical function to improve corrosion resistance, abrasion resistance and hardness, and increase the reflective ablity and beautifulness, etc. This process can release a kind of mist containing chromic acid, so if we do not use inhibitors or effective control measures to eliminate chromium fog, workers may be exposed to chromium. In recent years, with protective measures of improving, high concentration of chromic acid mist has been rare, but long-term effect such as cancer, teratogenic and mutation which caused by low concentration chromic acid mist has attracted people's attention. Electroplating has relation with increased risk rate of lung cancer, skin ulcer and septal perforation can also occur in this industry, and the possibility of skin and respiratory tract allergy still exists. So, this study was to evaluate the potential health effects related to chronic Cr(VI) exposure.157 electroplating workers from 25 electroplating factories and 93 non-chromate exposure subjects without exposure to other known physical or chemical genotoxic agents were recruited in Hangzhou, China. Subjects with abnormal liver or kidney function and suffering from other chronic diseases were excluded in the study. Epidemiological investigation questionnaires were conducted on electroplating workers and control subjects, respectively. Short-term sampling in the electroplating workplace was conducted according to a Standard of Industrial Hygiene in China (GBZ159-2004). Cr (VI) concentration in erythrocytes was measured by graphite furnace atomic absorption spectrometry, and Triton X-100 was used to make the red blood cells to release chromium. DNA damage was evaluated with an alkaline single cell gel electrophoresis (comet assay) in peripheral lymphocytes and concentration of 8-OHdG in urine was determined with ELISA kit, which is one of the major oxidative adducts formed by radical induced damage to DNA. Nine SNPs were included in base excision repair genes, nucleotide excision repair genes and metabolic enzyme gene to study the relation of DNA damage and genetic susceptibility. Genotypes of XRCC1 Arg194Trp and Arg399Gln were identified by PCR-RFLP, genotypes of OGG1 Ser326Cys,ERCC1 C8092A,ERCC6 Gly399Asp,ERCC5 His1104Asp,XPD Lys751Gln,XPC Lys939Gln and GSTP1 Ile105Val were determined by the TaqMan probes.The workshops of electroplating enterprises in this investigation were poorly equipped. And poor ventilated workshops could be harmful to electroplating workers. Educational level of electroplating workers culture level was low (85.35% below middle cultural degree), and most workers were lack of awareness of self protection. In electroplating workers, the median of Cr(Ⅵ) concentration (μg/L) in erythrocytes was 4.41(0.93,14.98), which was about two times higher than that in control subjects (1.54(0.14,4.58), P<0.001). After stratified by potential confounding factors such as gender, age, smoking status and alcohol consumption, significant differences were still existed between electroplating workers and control subjects, except for the subjects of age less than 30 years old (P=0.11).The median of tail length in electroplating workers was11.77 (3.46-52.19), the median of tail DNA% was 3.69(0.65-16.20), the median of Olive tail moment wasl.13 (0.14-6.77), and the differences between electroplating workers and control subjects were significant (P<0.001). Urinary 8-OHdG concentration was 13.65 (3.08,66.30)μg/g creatinine in electroplating workers and 8.31 (2.94,30.83)μg/g creatinine in control subjects. Their difference was also significant (P<0.001). After stratified by gender, age, smoking status, and alcohol consumption, the differences in tail length, tail DNA%, Olive tail moment and urinary 8-OHdG concentration still existed between two groups(P<0.05). After controlled for gender, age, smoking status, and alcohol consumption, the occupational Cr(Ⅵ) exposure was significantly positively associated with the Cr(Ⅵ) concentration in erythrocytes (μg/L), tail length, tail DNA%, Olive tail moment and urinary 8-OHdG concentration (μg/g creatinine) (P<0.001). The Cr (Ⅵ) concentration in erythrocytes (μg/L) was positively associated with tail length, tail DNA%, Olive tail moment (P<0.05). However, statistically significant association between Cr(VI) concentration in erythrocytes and urinary 8-OHdG was not found.The results showed level of DNA strand breaks of mutation type carriers of XRCC1Arg399Gln was higher than that in wild type, and SNPs of XRCC1Arg399Gln had significantly positively correlation with Olive tail moment. The effect of interaction between exposure and ERCC6-399 mutation type had statistical significant on Olive tail moment (P<0.05). The effect of interaction between OGG1Ser326Cys and ERCC1-8092 mutation type, ERCC5-515 and ERCC6-399 mutation type, XPD751 respectively with XRCC1-194, ERCC5-515,ERCC6-399 mutation type had statistical significant on urinary 8-OHdG(P<0.05).These results showed that the average level of chromium concentration in the air of occupational environment was higher than the national occupational health standards (0.05mg/m3), and Cr(VI) concentration in erythrocytes of electroplating workers was higher than that in control subjects. Hexavalent chromium pollution existed in electroplating process. Level of DNA strand breaks and concentration of urinary 8-OHdG of electroplating workers were higher than those in control subjects, so occupational hexavalent chromium exposure could induce DNA damage. XRCC1 Arg399Gln was the genetic susceptibility biomarker of electroplating workers. The interaction between exposure and NER, and the interaction between DNA excision repair pathways and metabolic enzyme genes might play important roles in DNA damage repair of electroplating workers.
Keywords/Search Tags:Hexavalent chromium, Occupational exposure, Genetic susceptibility
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