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.

Concomitant alterations in distribution of 70 kDa heat shock proteins, cytoskeleton and organelles in heat shocked 9L cells.

Maintenance of cell architecture and positioning of organelles are major functions of the cytoskeleton. On the other hand, induction of heat shock proteins (HSPs) and reorganization of the cytoskeleton are the most significant changes in heat-shocked mammalian cells. We examine the alterations in HSP70 and its constitutively expressed cognate, HSC70, as well as the cytoskeleton and organelles in 9L rat brain tumor cells upon heat shock. We employed fluorescence microscopy and scanning electron microscopy to follow these changes. Levels of HSP70s were quantified by Western blotting. Accumulation of HSC70 was more transient and the protein translocated to and subsequently exited from the nucleus more rapidly than HSP70. Changes in actin microfilaments include the nuclear localization of actin fraction and disappearance of cytoplasmic microfilament bundles, while the cortical actin microfilaments were almost unaffected. Furthermore, microtubules retracted slightly from the cell periphery but remained largely unchanged. In contrast, the intermediate filaments collapsed into the perinuclear region. The mitochondria converted from filamentous into granular forms and clustered in a region overlapping with the collapsed intermediate filaments. All of the above alterations are reversible and largely reverted after 8 h of recovery. The effect on Golgi organization was very transient and the apparatus assumed a normal appearance within 4 h after the heat treatment. The ER, on the other hand, was totally unaffected by the heat treatment. These observations help correlate the sequential events following a stress like heat shock and suggest possible physiological functions of these essential constituents of a cell under stress.

Glutathione S-transferase mu genotype, diet, and smoking as determinants of sister chromatid exchange frequency in lymphocytes.

Polymorphisms in inherited metabolic traits and intake of dietary antioxidants have been reported to be associated with risk for the development of lung cancer in smokers. This increased risk of lung cancer is presumably attributable to the accumulation of DNA damage. We conducted a study to investigate whether genetic metabolic variants and antioxidant consumption affected the sister chromatid exchange (SCE) level in lymphocytes. Study subjects were 78 friends and spouses of cases from a case-control study of lung cancer designed to investigate the association of metabolic polymorphisms with lung cancer. The metabolic traits studied included glutathione S-transferase class mu and variants of P-450 isoenzymes CYP1A1 and CYP2D6. Intake of antioxidants including vitamins A, C, and E and selenium was determined through the administration of a validated, semiquantitative food frequency questionnaire. Detailed information on smoking, family history of cancer, medical history, and environmental and occupational exposures was also obtained in an interviewer-administered questionnaire. Smoking status was found to be significantly associated with SCE frequency. In addition SCE frequency decreased with the period of time since quitting smoking. The presence of one or more glutathione S-transferase class mu alleles was associated with significantly lower SCE. Higher intake of vitamin A and selenium was also inversely associated with SCE level. Thus, the results suggest that glutathione S-transferase class mu and the intake of vitamin A and selenium may modulate the accumulation of chromosomal damage in lymphocytes.

Mutations in the p53 gene in lung cancer are associated with cigarette smoking and asbestos exposure.

It has been proposed that the patterns of mutations in the p53 tumor suppressor gene will provide clues to the mechanisms of cancer occurrence. Cigarette smoking is known to be the greatest risk factor for lung cancer. Epidemiological evidence has also implicated radon and asbestos as exposures that significantly increase this disease risk; asbestos exposure synergistically enhances the lung cancer risk of smokers. Previous studies of the mutational spectra of the p53 gene in lung cancer have shown cigarette smoke and radon exposure to be associated with the induction of particular lesions or classes of lesions. We have investigated the p53 gene in surgically resectable lung cancers in 85 patients from the Massachusetts General Hospital. We found 25 (29%) patients to have somatic p53 mutations in their tumors. The patients with p53 mutations who were current smokers were significantly older (75.1 versus 59.8 years; P < 0.01 and had smoked for significantly more years (56.8 versus 41.2 years; P < 0.01) than had those without p53 changes. Consistent with other reports, we observed a large number (40%) of G:C to T:A transversion mutations, noting that their occurrence increased with increasing cumulative exposure to cigarette smoke. Interestingly, we also found that p53 mutations occurred significantly more frequently in patients with a history of occupational exposure to asbestos [3 of 60 (5%) for patients without p53 mutations versus 5 of 25 (20%) of those with p53 mutations; P < 0.05].(ABSTRACT TRUNCATED AT 250 WORDS)

A piezoelectric quartz crystal sensor for the determination of coagulation time in plasma and whole blood.

A Peizoelectric Quartz Crystal (PQC) system possessing an adequate sensitivity to a slight viscosity change is employed to monitor the blood coagulation. In the case of an anticoagulated plasma specimen, prothrombin time (PT) was determined by the PQC sensor on the basis of the introduction of tissue thromboplastin (TF) and calcium ion. Discussing the PQC data statistically, we found that at 90% of the total frequency shift (delta f) the best linear relationship in a double-logarithmic plot of PT versus TF concentration in the range of 5.466-22.311 unit/ml is shown. The PQC result was compared with commercial optical coagulometry and showed a good linear correlation (ca. 0.98). The clotting and recalcification of whole blood were also studied by the PQC system. The testing time for one measurement could be completed within 20 min. and had a good agreement with that obtained conventionally.

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.

Plasma levels of antioxidant vitamins, selenium, total sulfhydryl groups and oxidative products in ischemic-stroke patients as compared to matched controls in Taiwan.

The possible involvement of oxidative damage and antioxidant protection has been suggested in the pathogenesis of stroke which is the second-leading cause of death in Taiwan. In this study we investigated the relationship between ischemic stroke and plasma status of antioxidants and oxidative products. Plasma levels of vitamin A, alpha-tocopherol, carotenoids, selenium (Se), total SH groups (T-SH), thiobarbituric acid-reactive substances (TBARS) and protein carbonyl, a marker of protein damage, were determined in ischemic-stroke patients (n = 36, blood sampled within 24 hrs after the clinical event) in comparison with 21 matched controls. The cholesterol-adjusted carotenoids and vitamin E were significantly lower (P < 0.05) in the plasma of ischemic-stroke patients than those of the controls. TBARS were higher (P < 0.05) in the patients than in the controls but Se, T-SH and protein carbonyls were not significantly different between the two groups. Separation of the patients into small-artery ischemic stroke (SAIS, n = 17) and large-artery ischemic stroke (LAIS, n = 19) groups revealed that both carotenoids/cholesterol and vitamin E/cholesterol ratios were significantly lower in both LAIS and SAIS groups than the controls (n = 21) while vitamin A/cholesterol was not different among the three groups. TBARS were only significantly higher in the LAIS group. The results demonstrated that, within 24 hrs after the clinical event, the acute-ischemic stroke patients had lowered levels of cholesterol-adjusted carotenoids and alpha-tocopherol but elevated levels of TBARS in the plasma as compared to the matched controls. It remains to be resolved as to whether enhanced lipid peroxidation is a cause or a result of lowered antioxidants in ischemic stroke.

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.

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.

Increased micronucleus frequency in lymphocytes from smokers with lung cancer.

We investigated whether lung cancer was associated with an increased micronucleus (MN) frequency in lymphocytes in a case-control study. Epidemiological data were obtained by an interviewer-administered questionnaire and included information on smoking history, intake of dietary micronutrients, general medical history, environmental and occupational exposures to mutagens and carcinogens, and family history of cancer. A modified cytokinesis-block method was used to determine individual MN frequency. Polymorphisms in glutathione S-transferase class mu were determined by PCR analysis. Overall, 55 controls and 42 cases were studied. MN frequency in cases and controls was not associated with age, smoking, metabolic genetic polymorphisms, environmental and occupational exposures, or medical history. Female controls had a significantly higher MN frequency than male controls (p = 0.05). Overall, MN frequency was significantly higher in cases than in controls (p < 0.01). Twenty-four cases (57%) had an MN frequency higher than the upper 95% confidence interval of the mean value for controls (11.5 MNs/1000 binucleated cells). Further analysis showed that, cases who were current and former smokers had significantly higher MN frequencies than controls (p = 0.04); this difference was not seen in the group that had never smoked. The significantly higher MN frequency among cases with a history of smoking may be attributable to the presence of lung neoplasm per se or to the interaction of smoking with endogenous factors associated with the development of lung cancer.

Mutant frequency at the hprt locus in human lymphocytes in a case-control study of lung cancer.

A clonal assay to determine the mutant frequency (MF) at the hypoxanthine-guanine phosphoribosyl transferase (hprt) locus in human lymphocytes has been used by a number of investigators to study exposure to mutagens and carcinogens in a variety of populations. We have studied hprt MF in 106 subjects (40 controls and 66 cases) enrolled in a case-control investigation of lung cancer. Epidemiological data collected included smoking history, intake of dietary micronutrients, and occupational and environmental exposures as well as medical history, all obtained from an interviewer-administered questionnaire. All subjects were also genotyped for the known polymorphism in glutathione S-transferase class mu (GST-mu). In analysis of cases and controls, hprt MF was not associated with age, smoking, the polymorphism in GST mu, dietary intake, occupational exposures, family history of cancer or usage of medications. Since MF and cloning efficiency (CE) are not independent when CE is low, further analysis in cases and controls with a CE greater than or equal to 30% (27 cases and 22 controls) was also conducted. In analysis of controls, hprt MF increased with age and was inversely associated with intake of folate and vitamins A and C. The presence of lung cancer was not associated with hprt MF. Thus, our study supports the previous observation that dietary components may affect the MF at the hprt locus.

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.

Comparison of sister chromatid exchange frequency in peripheral lymphocytes in lung cancer cases and controls.

Cytogenetic alterations have been associated with the occurrence of many cancers. However, limited data exist to address whether increased chromosomal changes in surrogate normal tissue are similarly associated with malignancy. As part of an ongoing case-control study of lung cancer, we have studied the factors that affect sister chromatid exchange (SCE) frequency in lymphocytes from lung cancer patients. Further, we sought to investigate whether the factors that affect SCE frequencies were comparable in lung cancer cases and controls. Cases had newly diagnosed, operable primary lung cancer. Controls were friends and spouses of cases. Detailed information on smoking, family history of cancer, medical history, and environmental and occupational exposures was obtained in an interviewer-administered questionnaire. Intake of antioxidants was also determined through the administration of a validated semiquantitative food frequency questionnaire. Metabolic traits studied included the polymorphic glutathione-S-transferase class mu (GST-mu) and variants of P450 isoenzymes CYP1A1 and CYP 2D6. Overall, 78 cases and 78 controls were included in the analysis. Although there was a small number of lung cancer patients who had never smoked in the study (9% of cases), these patients had higher SCE frequencies than current or former smokers. This suggests that factors associated with genomic instability may also play a role in the pathogenesis of lung cancer. The best fit model for SCE frequency, which had been previously generated from control data alone, included age, gender, smoking, GST-mu, and vitamin A intake. However, when this model was applied to lung cancer patients, smoking was not associated with an elevated SCE frequency. Thus, it is not clear that SCE frequency data in prevalent lung cancer cases and controls are comparable.

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.

Plasma Asp13-Ki-ras oncoprotein expression in vinyl chloride monomer workers in Taiwan.

Vinyl chloride (VC) workers are known to be at risk for development of liver angiosarcoma, a rare tumor. Previously, more than 80% of VC workers with liver angiosarcoma have been found to have an Asp-13 c-Ki-ras oncogene mutation, and more than 50% of VC-exposed workers without liver tumors were found to have Asp13-Ki-ras oncoprotein in their plasma. Some workers in Taiwan had also been exposed to VC, and some have contracted liver tumors. In this study, we used enhanced chemiluminescence Western blotting to detect Asp13-p21-Ki-ras in the sera of VC-exposed workers in Taiwan. There were 14 of 113 (12.4%) VC workers positive for the Asp13-Ki-ras oncoprotein in plasma, but 0 of 18 controls were positive. There were 10 of 69 (14.5%) plasma-positives among the more highly exposed (> 1000 ppm-months) workers and 4 of 48 (9.1%) plasma-positives among the lesser exposed (< or = 1000 ppm-months). Compared with the unexposed controls, the odds ratios (and 95% confidence intervals [CI]) for plasma-positivity were 4.11 (95% CI = 0.21, 80.4) in the lower-exposed workers and 6.53 (95% CI = 0.37, 116.9) in the higher-exposed workers, and there was a linear trend between exposure and plasma-positivity (P = 0.073). After adjusting for age and drinking status, the odds ratios (and 95% CIs) were 1.64 (95% CI = 0.17, 15.8), and 2.65 (95% CI = 0.42, 16.8), respectively, and there was a significant linear trend between exposure and plasma-positivity (P = 0.048). In summary, Asp13-Ki-ras oncoprotein can be found in the plasma of VC workers in Taiwan, and a significant dose-response relationship exists between plasma oncoprotein expression and VC exposure.

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.

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.

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).

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.