Redox potential of tea infusion as an index for the degree of fermentation.

Redox potential of tea infusion is suggested as an index for the extent of tea fermentation. The potential was measured between platinum and Ag/AgCl electrode pair with a voltmeter with high input impedance (>1000 Gohms). Phosphate buffer (10 mM, pH 7.0) was used to extract the infusion and served as the supporting electrolytes for the electrochemical measurement. The reliability (the Nernst's behavior) for redox potential measurement was verified with a standard redox couple, ferricyanide/ferrocyanide. Tentative interferences from dissolved oxygen and the major coexisting reducing chemical, ascorbate, were discussed. Redox potential showed strong correlation with the fermentation process during indoor withering process. Eleven kinds of tea with different fermentation extents including Sencha, Pilochun, Pouchong, Formosa oolong tea, Lipton green tea, Lipton black tea, and Taiwanese black tea were tested.

Abnormal liver function associated with occupational exposure to dimethylformamide and glutathione S-transferase polymorphisms.

Dimethylformaide (DMF) is a major solvent predominately used in synthetic leather and resin production. Many human and animal studies have linked the cause of hepatoxicity to DMF. Previously, the authors demonstrated the significant dose-response relationship between abnormal liver function tests and DMF exposure and the interaction with hepatitis B virus (HBV) infection in Taiwanese workers. Because the toxic effect of various chemicals can be modified by metabolic traits, the study also investigated the influence of the glutathione S-transferases (GSTM1 and GSTT1) on the toxic effect of DMF. The average DMF exposure concentration was 23.87 ppm (range 5.2-86.6 ppm) in the high-exposure (>/=5 ppm) group and 2.41 ppm (range 0.9-4.3 ppm) in the low-exposure (<5 ppm) group. There were 13 of 44 (29.6%) abnormal liver function tests (elevations of either glutamate oxaloacetate transaminase (GOT) or glutamate pyruvate transaminase (GPT)) among the high DMF exposure workers, two of 22 (9.1%) abnormal liver function tests among the low DMF exposure workers. Chronic liver disease as determined by ultrasonography was present in seven of 44 (15.9%) high DMF exposure workers, and 0 of 22 (0%) low DMF exposure workers. There were 11 of 34 (32.4%) abnormal liver function tests among the GSTT1 null genotype workers, and four of 32 (12.5%) abnormal liver function tests among the GSTT1-positive genotype workers. Compared with the low DMF exposure workers, the adjusted odds ratio and 95% confidence intervals for abnormal liver function tests was 6.78 (0.94-48.7) for the high DMF exposure workers. Compared with the GSTT1-positive genotype workers, the adjusted odds ratio and 95% confidence intervals for abnormal liver function tests was 4.41 (1.15-16.9) for the GSTT1 null genotype workers. Compared with the low DMF group with GSTT1-positive genotype workers, the odds ratio (adjusted for HBV status) of abnormal liver function test was 12.38, 95% CI=(1.04-146.9) for the high DMF group with GSTT1 null genotype workers. This study indicates that abnormal liver function and chronic liver disease are associated with DMF exposure, and there are more than multiplicative interaction effects on abnormal liver function tests between the DMF exposure and the GSTT1 genotype.

Prolonged menstrual cycles in female workers exposed to ethylene glycol ethers in the semiconductor manufacturing industry.

BACKGROUND: It has been shown that female workers exposed to ethylene glycol ethers (EGEs) in the semiconductor industry have higher risks of spontaneous abortion, subfertility, and menstrual disturbances, and prolonged waiting time to pregnancy. AIMS: To examine whether EGEs or other chemicals are associated with long menstrual cycles in female workers in the semiconductor manufacturing industry. METHODS: Cross-sectional questionnaire survey during the annual health examination at a wafer manufacturing company in Taiwan in 1997. A three tiered exposure-assessment strategy was used to analyse the risk. A short menstrual cycle was defined to be a cycle less than 24 days and a long cycle to be more than 35 days. RESULTS: There were 606 valid questionnaires from 473 workers in fabrication jobs and 133 in non-fabrication areas. Long menstrual cycles were associated with workers in fabrication areas compared to those in non-fabrication areas. Using workers in non-fabrication areas as referents, workers in photolithography and diffusion areas had higher risks for long menstrual cycles. Workers exposed to EGEs and isopropanol, and hydrofluoric acid, isopropanol, and phosphorous compounds also showed increased risks of a long menstrual cycle. CONCLUSIONS: Exposure to multiple chemicals, including EGEs in photolithography, might be associated with long menstrual cycles, and may play an important role in a prolonged time to pregnancy in the wafer manufacturing industry; however, the prevalence in the design, possible exposure misclassification, and chance should be considered.

Emerging epidemic in a growing industry: cigarette smoking among female micro-electronics workers in Taiwan.

OBJECTIVE: To explore the emerging tobacco epidemic in female workers in the growing micro-electronics industry of Taiwan. METHODS: Workers were surveyed regarding their smoking status, sociodemographics and work characteristics. In total, 1950 female employees in two large micro-electronics companies in Taiwan completed the survey. RESULTS: Approximately 9.3% of the female employees were occasional or daily smokers at the time of the survey. The prevalence of smoking was higher in those aged 16-19 years (20.9%), those not married (12.9%), those with a high school education or less (11.7%), those employed by Company A (11.7%), shift workers (14.3%), and those who had been in their present employment for 1 year or less (13.6%). Results of multivariate adjusted logistic regression indicated that younger age, lower level of education, shorter periods of employment with the company and shift working were the important factors in determining cigarette smoking among the study participants. The odds ratio of being a daily smoker was similar to that of being a current smoker. Marital status was the only significant variable when comparing former smokers with current smokers. CONCLUSIONS: Smoking prevalence in female workers in the two micro-electronics companies studied was much higher than previous reports have suggested about female smoking prevalence in Taiwan and China. We suggest that smoking is no longer a 'male problem' in Taiwan. Future smoking cessation and prevention programmes should target young working women as well as men.

Synergistic effect of hepatitis virus infection and occupational exposures to vinyl chloride monomer and ethylene dichloride on serum aminotransferase activity.

AIMS: To study the synergistic effect of occupational chemical exposure and hepatitis virus infection on serum aminotransferase activity. METHODS: A total of 568 male workers who were employed in five polyvinyl chloride (PVC) or four vinyl chloride monomer (VCM) manufacturing factories were studied. Information relating to current job title, alcohol consumption, and cigarette smoking was obtained. Exposure level of chemical mixtures was classified by hygienic effect (a summation of personal time weighted average/reference permissible exposure level of each chemical) into high, moderate, and low exposure groups. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT), hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), and anti-hepatitis C antibody were assayed. RESULTS: Hepatitis virus infection and increased body mass index were associated with abnormal serum aminotransferase activity. In workers with hepatitis virus infection, those with high exposure had a higher prevalence of abnormal AST and ALT compared to low exposure; among those without hepatitis virus infection, the differences of prevalence of abnormal AST and ALT were not significant between different chemical exposure groups. There was a significant trend of increasing risks of increased AST and ALT in moderate and high exposure groups with hepatitis virus infection. Such a synergistic effect was more prominent among HBeAg-positive workers. CONCLUSIONS: Mixed exposures to 1,2-ethylene dichloride and VCM have a positive synergistic effect with hepatitis virus infection on liver damage. Assessment of fitness for work should be considered in workers with hepatitis B and C infection, when they have potential exposure to hepatotoxins in the workplace.

Why can't Chinese Han drink alcohol? Hepatitis B virus infection and the evolution of acetaldehyde dehydrogenase deficiency.

An aldehyde-dehydrogenase (ALDH2) deficiency is a biological curb on excess alcohol-drinking. This enzyme deficiency is very common amongst Oriental people while it is relatively rare for most other populations. We observe that there is good geographical correlation between the prevalence of the mutant ALDH2*2 alleles and hepatitis B virus (HBV) infections. Populations that demonstrate a high ALDH2*2 prevalence are all located in HBV-endemic areas. Further, studies have shown that HBV and alcohol drinking exhibit a synergistic effect upon liver cirrhosis and cancer. A shorter life span for those with HBV infection and heavy alcohol consumption may result in a selection of the ALDH2*2 gene. We postulate that there may be patterns of evolutionary adaptation for ALDH2 deficiency in certain HBV-endemic areas and that these adaptations can produce differences in human alcohol-drinking capability.

An increased standardised mortality ratio for liver cancer among polyvinyl chloride workers in Taiwan.

AIMS: To determine the standardised mortality ratio (SMR) corresponding to different causes of death in workers from polyvinyl chloride polymerisation factories in Taiwan. METHODS: Retrospective cohort study of workers from six polyvinyl chloride polymerisation factories in Taiwan. A total of 3293 male workers who had been employed for at least one year during the period 1 January 1950 to 31 December 1992, and were alive on 1 January 1985 were included for analysis. Using data acquired from Taiwan's National Mortality Registry, it was found that 144 of these workers died during the period 1985-97. The follow up rate was 99% with a total number of person-years at risk of 40 557. RESULTS: SMR for all causes of death was 0.78, indicating a possible "healthy worker" effect. The SMR for liver cancer decreased with increasing age of first exposure to vinyl chloride monomer. This association was more prominent for workers who were first employed in the industry prior to 1970 (SMR 4.82). Medical records indicated that most liver cancers in this study were hepatocellular carcinoma. CONCLUSIONS: Polyvinyl chloride workers may experience a higher risk of developing liver cancer, particularly hepatocelluar carcinoma.

Urinary thiodiglycolic acid levels for vinyl chloride monomer-exposed polyvinyl chloride workers.

Thiodiglycolic acid (TdGA) is the major metabolite of vinyl chloride monomer (VCM) detected in human urine. Although urinary TdGA has been reported to be associated with ambient VCM exposure, the relationship between urinary TdGA and a low level of air VCM is not clear. Questionnaires were administered to 16 polyvinyl chloride manufacturing workers to obtain a detailed history of occupation and lifestyle. For each worker, personal air monitoring for VCM was performed and a time-weighted average for VCM exposure was calculated. The urinary TdGA levels at the end of a work shift, and at the commencement of the next shift, were also assessed for each worker. Urine analysis revealed that TdGA levels at the beginning of the next shift were higher than those at the end of that shift. Workers experiencing a VCM exposure greater than 5 ppm in air revealed a urinary TdGA level significantly greater than those experiencing a VCM exposure of less than 5 ppm (P < 0.05). The best fit of regression for urinary TdGA on air VCM was Y = 1.06 + 0.57X for urine collected at the commencement of the following work shift, where X is the air VCM concentration and Y is the urinary TdGA concentration (r2 = 0.65, P < 0.01). We conclude that the urinary TdGA level is best detected at the commencement of the next shift and that it can be used as an exposure marker for polyvinyl chloride workers when the air VCM level to which they are exposed is greater than 5 ppm.

Changes in the levels of nitric oxide synthase and protein kinase C gamma following kainic acid receptor activation in the rat spinal cord.

In this study, we evaluated the levels of nitric oxide synthase, both neuronal and induced (nNOS and iNOS, respectively), cyclooxygenase-1 and 2 (COX-1 and COX-2) and protein kinase C gamma (PKCgamma) and correlated these with algogenic behavior following spinal kainic acid (KA) receptor activation in rats. Thirty adult male Sprague-Dawley rats were randomly assigned into six groups (n=5). Groups A, B, and C received 0.5 g kainic acid intrathecally and were analyzed at 3, 6, 24 h after injection, respectively. Groups D, E, and F received saline and were analyzed at 3, 6, 24 h after injection, respectively. We observed for behavioral changes in the rats following intrathecal KA injection and analyzed the protein levels of NOS, COX and PKCgamma by Western blotting techniques. Importantly, we clarified the potential roles of PKCgamma in the regulation of nNOS and COX-2 following intrathecal injection with KA in the rat spinal cord. COX-2 protein was detected but not significantly changed in the lumbosacral spinal cord at 3, 6, and 24 h following intrathecal KA injection (P>0.05). In contrast, nNOS protein was detected at higher levels in comparison with normal spinal cord at 6 and 24 h after intrathecal administration of KA (P<0.05). PKCgamma also increased significantly at 3, 6, and 24 h after intrathecal KA injection when compared with the baseline level (P<0.05). On the other hand, COX-1 and iNOS were not detected in either normal or KA treated spinal cords. These results provide strong in vivo evidence to support the idea that nNOS but not COX-2, plays an important role in spinal KA receptor activation. Furthermore, up-regulation of PKCgamma is involved in KA induced algogenic behavior in rats.

Association between smoking, acetaldehyde dehydrogenase-2 1-1 status, and alcohol drinking among Taiwanese polyvinyl chloride workers.

To study the factors affecting alcohol consumption among Taiwanese workers, we conducted an investigation of the association between alcohol drinking and smoking, aldehyde dehydrogenase-2 (ALDH2) status, alcohol dehydrogenase-2 (ADH2) status, any history of abnormal liver function, and hepatitis B and C viral infection. The subjects included 207 male workers who had been followed-up with respect to liver function periodically since 1992. Information relating to current alcohol consumption and smoking habits was obtained by an interviewer-administered questionnaire in 1996, and any history of liver function and hepatitis B and C virus infection was obtained from previous medical surveillance. Genotypes of ALDH2 and ADH2 were determined by polymerase chain reaction/restriction fragment polymorphism assay. Results have revealed that smoking and ALDH2 1-1 status were associated with current alcohol consumption (respectively: odds ratio, 23.3; P < 0.01 and odds ratio, 14.5; P < 0.05). Neither a history of abnormal liver function nor a history of hepatitis B and/or C infection was associated with current alcohol consumption. It seems that only those with ALDH2 1-1 who are smokers consume alcohol. We conclude that smoking and inherited ALDH2 1-1 are the most important determinants of alcohol consumption. In addition to the medical advice of physicians in their yearly health check-ups, worksite health-promotion programs based on both alcohol consumption habits and smoking cessation should be instituted forthwith, particularly for those who demonstrate the potential for developing liver damage.

Abnormal liver function associated with occupational exposure to dimethylformamide and hepatitis B virus.

N,N-Dimethylformamide (DMF) has excellent solvent properties and is used intensively in the production of synthetic leather and resins. It has caused hepatoxicity in human and animal studies. Hepatitis B virus (HBV) and hepatitis C virus infections are reported to be the major causes of chronic liver diseases (including liver cirrhosis and liver cancer) in Taiwan. This study examined the dose-response relationship of the observed abnormal liver function among the DMF-exposed workers and the interactions among DMF, other chemical exposures, HBV infection, and potential confounders on liver abnormalities. The average DMF exposure concentration was 11.6 ppm (median, 5.9 ppm; range, 0.1 to 86.6 ppm); 65 of 176 workers (36.9%) had high (> 10 ppm) DMF exposure, 37 (21%) had middle (> 5 ppm, < or = 10 ppm) exposure, and 74 (42%) had low (< or = 5 ppm) exposure. There were 24 of 65 abnormal liver function test results (LFTs) (36.9%) (elevations of either glutamate oxaloacetate transaminase, glutamate pyruvate transaminase, or gamma-glutamyl transpeptidase) among the workers with high DMF exposure, 10 of 37 abnormal LFTs (27%) among workers with middle DMF exposure, and 11 of 74 abnormal LFTs (22%) among workers with low DMF exposure. Compared with the workers having low DMF exposure, the HBV, drinking, body mass index (BMI), sex, duration of employment, epichlorohydrin, and toluene exposure adjusted odds ratios (ORs) (and 95% confidence intervals [CIs]) for abnormal LFTs were 1.62 (0.61, 4.28) for workers with middle DMF exposure and 2.93 (1.27, 6.8) for those with high DMF exposure, and there was a significant dose response between DMF exposure and the prevalence of abnormal LFTs (P = 0.006). There were significant associations between abnormal LFTs and HBV carriers (adjusted OR: 3.11; 95% CI: 1.29, 7.5; P = 0.01) and between abnormal LFTs and increased BMI (adjusted OR: 2.2; 95% CI: 1.02, 4.72; P = 0.041). Ultrasonography showed significant associations between chronic liver diseases and HBV carrier status, increased BMI, and high cumulative (> 100 ppm-years) DMF exposure (respectively, adjusted OR: 9.58, 95% CI: 1.79, 51.4, P = 0.007; adjusted OR: 13.2, 95% CI: 1.32, 132, P = 0.025; and adjusted OR: 6.2, 95% CI: 1.14, 34.1, P = 0.032). Drinking and BMI were significantly associated with fatty liver (respectively, adjusted OR: 4.9, 95% CI: 1.39, 17.3, P = 0.012; and adjusted OR: 7.93, 95% CI: 1.6, 39.3, P = 0.01). In conclusion, this study demonstrated that (1) a significant dose-response relationship existed between liver function abnormalities and DMF exposure among workers in Taiwan, (2) HBV carrier status or increased BMI had synergistic effects with DMF in causing liver abnormalities (abnormal LFTs and clinical chronic liver diseases).

Increased lymphocyte sister chromatid exchange frequency in workers with exposure to low level of ethylene dichloride.

The genotoxicity of low-level exposure to ethylene dichloride (EDC) and vinyl chloride monomer (VCM) in humans is not clear. We used lymphocyte sister chromatid exchange (SCE) frequency as a parameter to investigate the genotoxicity of low level EDC and VCM in VCM-manufacturing workers. The SCE frequency was determined for 51 male workers with exposure to VCM and/or EDC and for 20 male workers devoid of such exposure. Epidemiological data were obtained by questionnaire, and included history of smoking, drinking, and any medication taken, as well as a detailed occupational history. Personal- and area-sampling and analysis were conducted in order to calculate the time-weighted average (TWA) contaminant-exposure level corresponding to different job categories. Moderate EDC exposure around 1 ppm corresponded to a significantly greater SCE frequency than was the case for the low EDC exposure group (p<0.01). However, VCM exposure of similar level was not associated with increased SCE. We conclude that EDC may cause genotoxicity at a relatively low level of exposure.

Dimethylacetamide, ethylenediamine, and diphenylmethane diisocyanate poisoning manifest as acute psychosis and pulmonary edema: treatment with hemoperfusion.

CASE REPORT: A 27-year-old man, employed by a synthetic fiber company, had been exposed to dimethylacetamide, ethylenediamine, and diphenylmethane diisocyanate in a confined space continuously for 4-6 hours per day for 3 days before admission. Hallucinations and delusions were noted at admission; pulmonary edema developed subsequently. The electroencephalogram showed diffuse moderate cortical dysfunction and slow waves at 4-7 Hz, 20-80 microV. Seizures, liver injury, and rhabdomyolysis were noted on the 4th hospital day. The patient was treated by hemoperfusion with a decrease in urine dimethylacetamide from 3,265 mg/g to 4 mg/g creatinine over 4 days. Serial urinary dimethylacetamide and electroencephalogram correlated with the clinical condition.

Association of protein phosphatase 2A with its substrate vimentin intermediate filaments in 9L rat brain tumor cells.

The importance of protein phosphatases in maintaining the integrity of intermediate filaments is supported by the fact that intermediate filaments would undergo a massive reorganization in cells treated with inhibitors of protein phosphatases 1 and 2A. Herein we used okadaic acid to investigate the differential roles of protein phosphatases 1 and 2A in the maintenance of intermediate filament integrity in 9L rat brain tumor cells. Protein phosphatase 2A activity was substantially inhibited after treatment with 400 nM okadaic acid for 2 h, whereas the activity of protein phosphatase 1 was only slightly affected. Furthermore, protein phosphatase 2A shows selective specificity toward phosphovimentin, which was immunologically precipitated from isotopically labeled and okadaic acid-treated cells. Further biochemical fractionation and microscopic studies revealed that vimentin intermediate filaments were colocalized with protein phosphatase 2A, but not protein phosphatase 1, in control cells. On okadaic acid treatment, vimentin filament disassembled and protein phosphatase 2A redistributed throughout the cytoplasm, suggesting that these two proteins separate from each other, whereas protein phosphatase 2A was inhibited. This working hypothesis was further supported by treatment with a low concentration (40 nM) of okadaic acid, which causes the same phenomenon. Taken together, our results showed that protein phosphatase 2A could be assigned to the intermediate filaments to serve the physiological role in maintaining the proper phosphorylation level of intermediate filaments in normal cells. This finding should pave the way for the elucidation of the regulatory mechanism of intermediate filament organization governed by protein phosphorylation.

Exposure to solvents in a synthetic leather manufacturing plant.

The objective of this study was to evaluate the exposure of synthetic leather workers to dimethylformamide (DMF), epichlorohydrin (ECH) and toluene, in a manufacturing plant. The correlation between biological and environmental monitoring for DMF was also investigated. Environmental monitoring of the three solvents included personal and area sampling based on time of day (morning and afternoon). Urine samples were taken at the end of the shift and urinary N-methylformamide (NMF) was then used to biologically monitor DMF levels. Results for solvent concentrations based on air sampling were considerably higher in area than in personal sampling. Of 41 area samples, 15 (36.6%) and five (12.2%) exceeded permissible exposure levels for DMF and ECH, respectively, compared with 22 (28.6%) and three (3.9%) based on 77 personal samples. Overall, urinary NMF concentrations were lower than the Biological Exposure Index (BEI) suggested by the American Conference of Governmental Industrial Hygienists (ACGIH). A significant correlation (r = 0.32; P < 0.05) was found between environmental and biological monitoring. Even though urinary NMF concentration was within permissible levels for Taiwan, the authors recommend that immediate measures be taken to decrease DMF and ECH concentrations in synthetic leather manufacturing plants.

Polymorphisms in the DNA repair genes XRCC1 and ERCC2 and biomarkers of DNA damage in human blood mononuclear cells.

Polymorphisms in several DNA repair genes have recently been identified, but little is known about their phenotypic significance. To determine whether variation in DNA repair genes is related to host DNA damage, we studied the association between polymorphisms in XRCC1 (codon 399) and ERCC2 (codon 751) and two markers of DNA damage, sister chromatid exchange (SCE) frequencies (n = 76) and polyphenol DNA adducts (n = 61). SCE frequencies were determined using a modified fluorescence-Giemsa method and polyphenol DNA adducts were determined using a P1-enhanced (32)P-post-labeling procedure. XRCC1 and ERCC2 genotypes were identified using PCR-RFLP. Mean SCE frequencies among current smokers who were homozygous carriers of the 399Gln allele in XRCC1 were greater than those in 399Arg/Arg current smokers. We also observed a possible gene-dosage effect for XRCC1 399Gln and detectable DNA adducts, and significantly more adducts among older subjects who were carriers of the 399Gln allele than in younger subjects with the 399Arg/Arg genotype. The polymorphism in ERCC2 was unrelated to SCE frequency or DNA adduct level. Our results suggest that carriers of the polymorphic XRCC1 399Gln allele may be at greater risk for tobacco- and age-related DNA damage.

Abnormal liver function in workers exposed to low levels of ethylene dichloride and vinyl chloride monomer.

We investigated whether exposure to ethylene dichloride (EDC) and vinyl chloride monomer (VCM) resulted in increased risk of liver damage. Epidemiological information, including occupational, medical, smoking, and drinking history, was obtained by interview from 251 male workers. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyltransferase (GGT) were used as indicators of liver damage. Exposure to moderate or low levels of ECD and VCM resulted in a higher risk of developing abnormal ALT levels than did exposure to lower levels of the chemicals. Results were similar for AST. GGT was not associated with EDC or VCM exposure. Combined exposure to EDC and VCM showed a dose-response relationship in association with abnormal ALT levels. We concluded that relatively low concentrations of VCM and EDC cause liver damage.

Exposure to epichlorohydrin and dimethylformamide, glutathione S-transferases and sister chromatid exchange frequencies in peripheral lymphocytes.

Workers in epoxy resin, synthetic leather, and printed circuit board manufacturing plants are exposed to epichlorohydrin (ECH), or dimethylformamide (DMF), or both. ECH, an alkylating agent, has been shown to cause malignancy in animals, but its genotoxicity in humans is unclear. DMF is a well-known hepatotoxic chemical, although evidence of its genotoxicity in humans is also limited. In this study, we examined the effects of exposure to ECH and DMF on sister chromatid exchange (SCE) in plant workers, in order to examine the genotoxicity of these two agents. Because the genotoxicity of certain agents can be modulated by metabolic traits, we also investigated influence of the glutathione S-transferase (GST) micro (GST M1) and GST theta (GST T1) genes on the genotoxicity of ECH and DMF. A total of 85 male plant workers were included in this study. The subjects were divided into five exposure groups, based on their job titles and the airborne ECH and DMF concentrations in their areas of work. A questionnaire was administered to obtain detailed occupational, smoking, alcohol consumption, and medication histories. Standardized cytogenetic methods were used to determine the frequency of sister chromatid exchange (SCE) in peripheral blood lymphocytes. GST M and GST T1 genotypes were identified using polymerase chain reaction (PCR). In analysis, smoking was significantly associated with increased SCE frequency (P<0.01). Workers with high ECH exposure also had significantly higher SCE frequencies than those with low or no ECH exposure (P<0.05). However, DMF exposure was not associated with SCE frequency. The GST M1 null genotype was also found to be associated with an increased SCE frequency (P = 0.06). We conclude that ECH exposure may be associated with genetic toxicity and that DMF does not appear to be genotoxic.

Plasma p53 protein and anti-p53 antibody expression in vinyl chloride monomer workers in Taiwan.

Vinyl chloride (VC) workers are known to be at risk for development of angiosarcoma of the liver (ASL), a rare tumor. Previously, a study of p53 gene mutations in tumors of VC-exposed workers found that 50% of liver angiosarcomas contained such mutations. Mutant p53 oncoprotein and anti-p53 antibodies can also be found in the sera of ASL patients and VC-exposed workers without cancer. Workers in Taiwan have also been exposed to VC, and some have contracted liver tumors. In this study, we used enzyme-linked immunosorbent assays to detect mutant p53 protein and anti-p53 antibodies in the plasma of VC-exposed workers in Taiwan. Thirty-three of 251 (13.2%) VC-workers tested positive for the p53 overexpression (10% with positive mutant p53 protein and 3.6% with positive anti-p53) in their plasma, but only 2 of 36 controls (5.6%) tested positive (2.8% with positive mutant p53 protein and 2.8% with positive anti-p53). There was a significant association between cumulative VC exposure concentration and positive p53 expression (P = 0.032) among VC workers after we adjusted for age, hepatitis, drinking, and smoking status. In summary, P53 overexpression (mutant p53 protein or anti-p53 antibody) can be found in the plasma of VC workers in Taiwan, and a significant dose-response relationship exists between plasma p53 overexpression and VC cumulative exposure concentration.

Effects on sister chromatid exchange frequency of aldehyde dehydrogenase 2 genotype and smoking in vinyl chloride workers.

Vinyl chloride monomer (VCM) is a human carcinogen. However, the exact mechanism of carcinogenesis remains unclear. VCM may be metabolized by cytochrome P450 2E1 (CYP2E1), aldehyde dehydrogenase 2 (ALDH2) and glutathione S-transferases (GSTs). Thus workers with inherited variant metabolic enzyme activities may have an altered risk of genotoxicity. This study was designed to investigate which risk factors might affect sister chromatid exchange (SCE) frequency in polyvinyl chloride (PVC) workers. Study subjects were 44 male workers from three PVC factories. Questionnaires were administered to obtain detailed histories of cigarette smoking, alcohol consumption, occupations, and medications. SCE frequency in peripheral lymphocytes was determined using a standardized method, and CYP2E1, GSTM1, GSTT1 and ALDH2 genotypes were identified by the polymerase chain reaction (PCR). Analysis revealed that smoking status and exposure to VCM were significantly associated with increased SCE frequency. The presence of ALDH2 1-2/2-2 genotypes was also significantly associated with an elevation of SCE frequency (9. 5 vs. 8.1, p<0.01). However, CYP2E1, GSTM1 or GSTT1 genotypes were not significantly associated with SCE frequency. When various genotypes were considered together, combination of CYP2E1 c1c2/c2c2 with ALDH2 1-2/2-2 showed an additive effect on SCE frequency. Similar results were also found for the combination of smoking with CYP2E1, or smoking with ALDH2. These results suggest that VCM workers with ALDH2 1-2/2-2 genotypes, who also smoke, may have increased risk of DNA damage.