OBJECTIVETo screen out serum differential proteins between vinyl chloride monomer (VCM)-exposed workers and healthy controls by proteomics and analyze the functions of differential proteins, and to provide a basis for elucidating the pathogenesis of diseases caused by VCM exposure and searching for the protein biomarkers.

METHODSFasting venous blood was collected from 125 VCM-exposed workers and 40 healthy controls according to accumulated exposure doses. Proteins were precipitated by acetone precipitation. These proteins were identified by 2D-nano LC-ESI-TOF/MS and quantified by isobaric tags for relative and absolute quantitation. The functions of differential proteins were analyzed by gene ontology.

RESULTSA total of 596 proteins were identified, including 194 quantified proteins. There were 21 differential proteins according to the screening criteria (19 upregulated proteins and 2 downregulated proteins), including complement, apolipoprotein, and glycoprotein. The functions of these differential proteins were binding, enzyme regulator activity, catalytic activity, and transporter activity, and they were involved in the biological processes including immune system process and response to stimulus.

CONCLUSIONThe complement, apolipoprotein, and glycoprotein identified in the proteomics may be related to liver injury caused by VCM exposure, and they could be used as candidate protein biomarkers of diseases caused by VCM exposure.

Biomarkers ; blood ; Blood Proteins ; analysis ; Humans ; Liver ; injuries ; Occupational Exposure ; Proteins ; metabolism ; Proteomics ; Vinyl Chloride ; toxicity

Recently, Ng et al. reported that the A:T > T:A substitutions, proposed to be a signature of aristolochic acid (AA) exposure, were detected in 76/98 (78%) of patients with hepatocellular carcinoma (HCC) from the Taiwan Province of China, and 47% to 1.7% of HCCs from the Chinese mainland and other countries harbored the nucleotide changes. However, other carcinogens, e.g., tobacco carcinogens 4-aminobiphenyl and 1,3-butadiene, air toxic vinyl chloride and its reactive metabolites chloroethylene oxide, melphalan and chlorambucil, also cause this signature in the genome. Since tobacco smoke is a worldwide public health threat and vinyl chloride distributes globally and is an air pollutant in Taiwan Province, the estimation of the patients' exposure history is the key to determine the "culprit" of the A:T > T:A mutations. Apparently, without estimation of the patients' exposure history, the conclusion of Ng et al. is unpersuasive and misleading.
Aristolochic Acids ; toxicity ; Carcinogens ; toxicity ; Carcinoma, Hepatocellular ; chemically induced ; genetics ; China ; Environment ; Humans ; Liver Neoplasms ; chemically induced ; genetics ; Mutation ; Taiwan ; Tobacco ; toxicity ; Vinyl Chloride ; toxicity

OBJECTIVETo explore the association between DNA damage induced by vinyl chloride monomer (VCM) and polymorphisms of DNA repair genes and xenobiotic metabolism genes of VCM.

METHODSComet assay was employed to detect DNA damage. Based on the status of DNA damage, the VCM exposure workers were divided into two groups: DNA damage group (75) and control group (75). Case-control design was used to investigate the association between the genetic polymorphisms and DNA damage induced by VCM. Genotypes of XRCC1 (Arg194Trp, Arg280His and Arg399Gln), XPD (Ile199Met, Asp312Asn and Lys751Gln) and CYP2E1 were identified by the PCR-RFLP. PCR assay was used to detect positive and null genotype of GSTT1 and GSTM1.

RESULTSUnivariate analysis showed that the CYP2E1 c1c2/c2c2 and XPD751 Lys/Gln and Gln/Gln genotypes were significantly associated with the increased levels of DNA damage, XRCCI 339 Arg/Gln and Gln/Gln genotypes were significantly associated with the decreased levels of DNA damage (P < 0.01, P < 0.05, respectively). Logistic regression analysis showed that there was significant association between the genotypes of XRCC1 194, XRCC1 399, XPD 751, CYP2E1 and DNA damages. A prominent risk decreasing of DNA damage was observed for those individuals possessing XRCC1 399Arg/Gln + Gln/Gln genotypes (OR: 0.35, 95%CI: 0.12 approximately 1.01, respectively); The results also showed that there were significant associations between CYP2E1 c1c2/c2c2 and DNA damage both in high and low VCM-exposed groups (OR: 2.57, 95%CI: 1.01 approximately 6.59 and OR: 2.57, 95%CI: 0.99 approximately 6.87).

CONCLUSIONCumulative exposure dose and genotypes of XRCC1 194, XRCC1 399, XPD 751 and CYP2E1 may modulate the DNA damage induced by VCM exposure.

Case-Control Studies ; Comet Assay ; DNA Damage ; drug effects ; Female ; Genetic Predisposition to Disease ; Genotype ; Humans ; Male ; Occupational Exposure ; Polymorphism, Single Nucleotide ; Vinyl Chloride ; toxicity ; Workplace

OBJECTIVETo explore the effect of vinyl chloride on reproductive and endocrine system of male rats.

METHODSMale SD rats were administered with vinyl chloride at dose of (0, 10, 100, 1000 mg/kg) for 14 and 28 days, respectively. The levels of testosterone (T), inhibin B, luteinizing hormone (LH), follicle stimulating hormone (FSH) and estradiol (E2) were measured in serum and testis homogenates. Histopathological examinations were performed for testis with electron microscopy.

RESULTSCompared with the control group after 14-day exposure, T and E2 serum levels of 1000, 100, 10 mg/kg groups decreased, InhB and LH levels of three dose groups increased. LH serum levels of 100 mg/kg increased significantly statistically compared with control group (P < 0.05). After 28-day exposure, T serum levels of 100, 1000 mg/kg groups were (10.90 +/- 1.56), (8.52 +/- 2.85) ng/ml respectively (P < 0.05), InhB serum levels of 100, 1000 mg/kg groups were (31.40 +/- 6.21), (28.39 +/- 5.67) pg/ml respectively. Both of T and InhB serum levels of 100, 1000 mg/kg groups decreased significantly (P < 0.05). Serum FSH levels of 10, 100, 1000 mg/kg groups decreased significantly compared with control group (P < 0.05). Compared with groups of 14-day exposure, serum InhB and LH levels of 10, 100, 1000 mg/kg groups decreased significantly statistically after 28 days. T and InhB testis levels of 100, 1000 mg/kg groups were 8.05 +/- 2.19),(6.75 +/- 1.94) ng/mg pro and (39.32 +/- 5.55), (35.53 +/- 8.71) pg/mg pro respectively, which decreased significantly compared with control group (P < 0.05). Leydig cell and Sertoli cell were damaged according to histopathological examinations.

CONCLUSIONVinyl chloride has adverse effects on reproductive and endocrine system of male rats and may change their serum and testis homogenate levels of hormones.

Animals ; Follicle Stimulating Hormone ; blood ; Leydig Cells ; ultrastructure ; Male ; Rats ; Sertoli Cells ; ultrastructure ; Testis ; drug effects ; metabolism ; Testosterone ; blood ; Vinyl Chloride ; toxicity

OBJECTIVETo explore the association between chromosomal damage induced by vinyl chloride monomer (VCM) and polymorphisms of xenobiotic metabolism genes and DNA repair genes.

METHODSCytokinesis-block micronucleus (CBMN) test was performed to detect chromosomal damage in peripheral lymphocytes of 402 VCM-exposed workers. Multiplex PCR was used to simultaneously amplify GSTM1 and GSTT1 genes, other genetic polymorphisms were performed using a PCR-RFLP technique.

RESULTSMultiple (adjusted) Poisson regression analysis showed that mean MN frequencies were significantly elevated for the intermediate (4000-40000 mg) and high (> 40000 mg) exposure groups as compared with the low exposure group (P = 0.003 and 0.03, respectively). For genetic polymorphisms, the exposed workers with CYP2E1 or XRCC1 Arg280His variance showed a higher CBMN frequency than their wild-type homozygous counterparts (P = 0.02); so did the workers with GSTP1 105Val/Val genotype or ALDH2 504Glu/Glu genotype than those with a combination of other genotypes (P = 0.01 and 0.003, respectively).

CONCLUSIONOur findings reveal that cumulative exposure dose of VCM and common genetic variants in genes, such as GSTP1, CYP2E1, ALDH2, XRCC1 Arg280His genotypes, are the major factors that modulate MN induction in VCM- exposed workers. Further study to investigate the relationship between individual characteristics and genetic susceptibility to VCM-caused chromosome damage is warranted, it is helpful for us to understand the mechanism of VCM metabolism, to find the biomarkers of susceptibility and to recognize the susceptible individuals in the primary prevention of VCM-caused damage.

Adult ; Chromosome Aberrations ; DNA Damage ; DNA Repair ; Female ; Genetic Predisposition to Disease ; Genotype ; Humans ; Male ; Micronucleus Tests ; Middle Aged ; Occupational Exposure ; Vinyl Chloride ; toxicity ; Young Adult

Occupational diseases may be defined only medically or scientifically, and even then, their definition is not simple. However, compensable occupational diseases involve the additional layer of legal systems and social welfare policies as well. Their multifaceted nature makes determining the work-relatedness of these diseases more complex. Korea has established standards for the recognition of occupational diseases in Schedule 5 of the Enforcement Decree of the Labor Standards Act, and specific criteria for the recognition of occupational diseases are listed in Schedule 3 of the Enforcement Decree of the Industrial Accident Compensation Insurance Act. The new list of compensable occupational diseases comprises 13 articles as an open-ended system. The newly added articles pertain to lymphohematopoietic (Article 5) and infectious diseases (Article 9), as well as diseases of other target organs. Furthermore, the article on liver diseases (Article 8) has been partially revised. The new act has been changed to clarify the meaning as it has been presented in recent research. It is necessary to achieve agreement among concerned parties, including experts from the legal, medical, and social domains to resolve the issues of work-relatedness, causation, notion of aggravation, and so on for preparing a list and a process that are more reasonable.
Adult ; Benzene/toxicity ; Communicable Diseases/*economics ; Dimethylformamide/toxicity ; Drug-Induced Liver Injury/economics ; Female ; Hematologic Diseases/chemically induced/*economics ; Humans ; Lead/toxicity ; Liver Diseases/*economics ; Male ; Middle Aged ; Occupational Diseases/*economics ; Republic of Korea ; Trichloroethylene/toxicity ; Vinyl Chloride/toxicity ; Workers' Compensation/*economics

OBJECTIVETo study DNA damages of liver cells in rats exposed to vinyl chloride monomer (VCM), and the expressions of DNA damage repair enzymes including O(6)-methyl guanine-DNA methyl transferase (MGMT), X-ray repair cross-complementing group 1 (XRCC1) and X-ray repair cross-complementing group 3 (XRCC3); and to explore the repair mechanism of DNA damage induced by VCM.

METHODSRats were exposed to VCM by intraperitoneal injection. DNA damages were detected by single cell gel electrophoresis (comet assay). The expressions of DNA damage repair enzymes were measured by immunohistochemical methods.

RESULTSThe percentages of comet cells in low, moderate, and high dose groups (11.75%, 12.38%, and 17.63%, respectively) were greater than that of control (5.67%). The latter two groups were significantly different from that of control (P < 0.05, P < 0.01). The expressions of MGMT and XRCC1 decreased, and XRCC3 increased with the dose of VCM increased. DNA damage was correlated with the expression of XRCC3 (r = 0.438, P = 0.067).

CONCLUSIONVCM can cause DNA damage of liver cells with dose-response relationship. DNA damage repair enzymes take part in the repairing of DNA damage induced by VCM.

Animals ; Carcinogens ; toxicity ; DNA Damage ; drug effects ; DNA Repair ; DNA-Binding Proteins ; genetics ; metabolism ; Dose-Response Relationship, Drug ; Liver ; cytology ; metabolism ; Male ; O(6)-Methylguanine-DNA Methyltransferase ; genetics ; metabolism ; Rats ; Rats, Sprague-Dawley ; Vinyl Chloride ; toxicity ; X-ray Repair Cross Complementing Protein 1