Evaluation of chemical-specific IgG antibodies in male workers from a urethane foam factory.

BACKGROUND: Plastic resins are complex chemicals that contain toluene diisocyanate (TDI) and/or trimellitic anhydride (TMA), which cause occupational allergies (OA), including respiratory allergies. Serum IgGs against TDI and TMA have been suggested as potential markers of the exposure status and as exploring cause of OA. Although TDI-specific IgG has been examined for suspected OA, TMA-specific IgG is not commonly evaluated in a urethane foam factory. This study therefore investigated both TDI- and TMA-specific IgGs in suspected OA patients and to evaluate the usefulness of the measurement of multiple chemical-specific IgG measurement for practical monitoring. METHODS: Blood samples were collected from two male workers who developed respiratory allergies supposedly caused by occupational exposure to TDI and/or TMA for the presence of TDI- and TMA-specific IgGs. In addition, blood samples from 75 male workers from a urethane foam factory, along with 87 male control subjects, were collected in 2014 and tested for the same IgGs in 2014. The presence and levels of TDI- and TMA-specific serum IgGs were measured using dot blot assays. RESULTS: We found that controls had mean concentrations of TDI- and TMA-specific IgGs of 0.98 and 2.10 µg/mL, respectively. In the two workers with respiratory allergies, the TDI-specific IgG concentrations were 15.6 and 9.51 µg/mL, and TMA-specific IgG concentrations were 4.56 and 14.4 µg/mL, which are clearly higher than those in controls. Mean concentrations of TDI- and TMA-specific IgGs in the factory workers were 1.89 and 2.41 µg/mL, respectively, and are significantly higher than those of the controls (P < 0.001 and P < 0.026 for TDI- and TMA-specific IgGs, respectively). CONCLUSION: The workers suspected of OA showed an evidently high level of TDI- and TMA-specific IgG, and these levels in workers at the urethane foam factory were also significantly higher than those in controls. In conclusion, the measurement of TDI- and TMA-specific IgG among workers using plastic resins is helpful to monitor their exposure status.

Changes of Working Responsibilities and Intentions of Industrial Physicians (Graduates of University of Occupational and Environmental Health, Japan) in a Comparison Between 2001, 2008 and 2015 Questionnaire Analyses.

For the purpose of understanding the current conditions of the duties of industrial physicians and the consciousness of graduates of the University of Occupational and Environmental Health, Japan (UOEH) engaged in industry, we performed a questionnaire survey in July, 2001 and July, 2008 and reported the results (J UOEH 2009 31: 281-91). A similar survey was carried out in July, 2015. We dispatched the questionnaire to industrial physicians and physicians in occupational health organizations who had graduated from UOEH and got the replies. The investigation asked about their career, their activities, and how they thought about their duties. We compared the three years and got the following results: 1) The ratio of respondents who were satisfied with the salary or official post was 38.3, 48.1, 65.4% in each investigation, respectively. 2) The ratio of the respondents whose official post and rank would not be promoted in the future was 25.3, 28.4, 32.3%, respectively. 3) The ratio of respondents satisfied with the relationship with the superior and the industrial health staff was 70.8, 80.3, 86.1%, respectively. The investigation performed every seven years since July, 2001 showed that the ratio of the graduates of UOEH whose official post and rank would not be promoted in the future had gradually increased, while the ratio of graduates who were satisfied with the relationship with the superior and the industrial health staff had also gradually increased.

ALDH2 Deficiency Promotes Ethanol-Induced Gut Barrier Dysfunction and Fatty Liver in Mice.

BACKGROUND: Acetaldehyde, the toxic ethanol (EtOH) metabolite, disrupts intestinal epithelial barrier function. Aldehyde dehydrogenase (ALDH) detoxifies acetaldehyde into acetate. Subpopulations of Asians and Native Americans show polymorphism with loss-of-function mutations in ALDH2. We evaluated the effect of ALDH2 deficiency on EtOH-induced disruption of intestinal epithelial tight junctions and adherens junctions, gut barrier dysfunction, and liver injury. METHODS: Wild-type and ALDH2-deficient mice were fed EtOH (1 to 6%) in Lieber-DeCarli diet for 4 weeks. Gut permeability in vivo was measured by plasma-to-luminal flux of FITC-inulin, tight junction and adherens junction integrity was analyzed by confocal microscopy, and liver injury was assessed by the analysis of plasma transaminase activity, histopathology, and liver triglyceride. RESULTS: EtOH feeding elevated colonic mucosal acetaldehyde, which was significantly greater in ALDH2-deficient mice. ALDH2(-/-) mice showed a drastic reduction in the EtOH diet intake. Therefore, this study was continued only in wild-type and ALDH2(+/-) mice. EtOH feeding elevated mucosal inulin permeability in distal colon, but not in proximal colon, ileum, or jejunum of wild-type mice. In ALDH2(+/-) mice, EtOH-induced inulin permeability in distal colon was not only higher than that in wild-type mice, but inulin permeability was also elevated in the proximal colon, ileum, and jejunum. Greater inulin permeability in distal colon of ALDH2(+/-) mice was associated with a more severe redistribution of tight junction and adherens junction proteins from the intercellular junctions. In ALDH2(+/-) mice, but not in wild-type mice, EtOH feeding caused a loss of junctional distribution of tight junction and adherens junction proteins in the ileum. Histopathology, plasma transaminases, and liver triglyceride analyses showed that EtOH-induced liver damage was significantly greater in ALDH2(+/-) mice compared to wild-type mice. CONCLUSIONS: These data demonstrate that ALDH2 deficiency enhances EtOH-induced disruption of intestinal epithelial tight junctions, barrier dysfunction, and liver damage.

Comparison of IgG against plastic resin in workers with and without chemical dermatitis.

BACKGROUND: There are many chemical sensitizers which cause allergy in the surrounding environment. However, the identification of substances causing allergy is difficult. We developed a new method to detect IgG which reacts against many kinds of chemical-human serum albumin (HSA) adducts at the same time. In this study, the diagnostic significance of the IgG was studied among workers of a company where a mass outbreak of chemical dermatitis had occurred after changing a plastic resin to a new one. METHODS: Eleven workers who handled the new plastic resin and suffered from dermatitis (case) and 9 workers who also handled the same resin in the same company but were free from dermatitis (control) were the subjects. Immunological dot blotting was carried out to detect serum IgG using originally prepared diagnostic antigens, comprising a mixture of HSA and the plastic resin or its components under various conditions. RESULTS: IgG against the plastic resin in use was detected in all workers who suffered from dermatitis. The prevalence of the IgG against the plastic resin was significantly higher in workers with than in those without dermatitis. On the other hand, IgG against its components (bisphenol A diglycidyl ether, m-xylylenediamine and butyl 2,3-epoxypropyl ether) was detected in a few workers with dermatitis. DISCUSSION: This suggests that IgG against chemical-HSA adduct reflects not only exposure but also causative chemicals of dermatitis. Our method to use a material itself as a hapten is practical and useful in the occupational field. CONCLUSION: It is suggested that IgG against chemicals is a useful marker of chemicals inducing dermatitis.

[University of Occupational and Environmental Health, Japan: 2013 alumni physician statistics].

The University of Occupational and Environmental Health, Japan (UOEH) is a publically funded medical school for occupational health physician and researchers. All students are funded through six years of medical school and commit to a nine-year health services of occupational medicine after graduation. Between 1984 and 2013, the number of physicians graduating from UOEH was 2,875. Of these, 473 were medical residents in our postgraduate residency programs and 526 were occupational health physicians affiliated with different companies. A total of 252 graduates became UOEH research/teaching staff, 219 obtained employment as physicians at Rousai hospital (hospital operated by Japan Labour Health and Welfare Organization), and 84 entered industrial hygiene and health check organizations. UOEH alumni are distributed throughout Japan in large workplaces/ business establishments. Many physicians continued in their job after the nine-year obligation, thus contributing to the increasing number of occupational health physicians during recent decades. We suggest that funding and postgraduate residency programs contribute to the increasing numbers of physicians, but further analysis needs to be done.

The effect of mask fit test on the association between the concentration of metals in biological samples and the results of time-weighted average personal exposure: A study on Japanese male welders.

OBJECTIVES: The mask fit test confirms whether the wearing condition of the wearer's face and the facepiece of the respirators are used appropriately. This study aimed to examine whether the results of the mask fit test affect the association between the concentration of metals related to welding fumes in biological samples and the results of time-weighted average (TWA) personal exposures. METHODS: A total of 94 male welders were recruited. Blood and urine samples were obtained from all participants to measure the metal exposure levels. Using personal exposure measurements, the 8-h TWA (8 h-TWA) of respirable dust, TWA of respirable Mn, and 8-h TWA of respirable Mn were calculated. The mask fit test was performed using the quantitative method specified in the Japanese Industrial Standard T8150:2021. RESULTS: Fifty-four participants (57%) passed the mask fit test. Only in the Fail group of the mask fit test, it was observed that blood Mn concentrations be positively associated with the results of TWA personal exposure after adjusting for multivariate factors (8-h TWA of respirable dust; coefficient, 0.066; standard error (SE), 0.028; P = 0.018, TWA of respirable Mn: coefficient, 0.048; SE, 0.020; P = 0.019, 8 h-TWA of respirable Mn: coefficient, 0.041; SE, 0.020; P = 0.041). CONCLUSIONS: The results clarify that welders with high concentrations of welding fumes in their breathing air zone are exposed to dust and Mn if there is leaking air owing to the lack of fitness between respirators and the wearer's face when using human samples in Japan.

Associations between welding fume exposure and neurological function in Japanese male welders and non-welders.

OBJECTIVES: There are some studies reporting the association between (manganese [Mn]) exposure to welding fume and neurological dysfunction. This study examined the relationship between Mn exposure and neurological behavior in Japanese male welders and non-welders using biological samples, which to date has not been assessed in Japan. METHODS: A total of 94 male welders and 95 male non-welders who worked in the same factories were recruited. The blood and urine samples were obtained from all the participants to measure Mn exposure levels. Neurological function tests were also conducted with all participants. The sampling of the breathing air zone using a personal sampler was measured for welders only. RESULTS: The odds ratios (ORs) for the Working Memory Index (WMI) scores were significantly higher among all participants in the low blood Mn concentration group than those in the high blood Mn concentration group (OR, 2.77; 95% confidence interval [CI], 1.24, 6.19; P = .013). The association of WMI scores and blood Mn levels in welders had the highest OR (OR, 3.73; 95% CI, 1.04, 13.38; P = .043). Although not statistically significant, a mild relationship between WMI scores and blood Mn levels was observed in non-welders (OR, 2.09; 95% CI, 0.63, 6.94; P = .227). CONCLUSIONS: The results revealed a significant positive relationship between blood Mn and neurological dysfunction in welders. Furthermore, non-welders at the same factories may be secondarily exposed to welding fumes. Further research is needed to clarify this possibility.

The effect of ethanol on the formation of N2-ethylidene-dG adducts in mice: implications for alcohol-related carcinogenicity of the oral cavity and esophagus.

The present study aimed to experimentally confirm that long-term alcohol drinking causes a high risk of oral and esophageal cancer in aldehyde dehydrogenase 2 (ALDH2)-deficient individuals. Aldh2 knockout mice, an animal model of ALDH2-deficiency, were treated with 8% ethanol for 14 months. Levels of acetaldehyde-derived DNA adducts were increased in esophagus, tongue and submandibular gland. Our finding that a lack of Aldh2 leads to more DNA damage after chronic ethanol treatment in mice supports epidemiological findings on the carcinogenicity of alcohol in ALDH2-deficient individuals who drink chronically.

[Necessary number of dedicated industrial physicians in Japan: evaluated from the establishment and enterprise census].

The required number of dedicated industrial physicians has been enacted by the Ministry of Health, Labour and Welfare in Japan. However, the number of workplaces requiring an appointment of industrial physicians is unknown, because of the lack of official publication from the Ministry of Health, Labor and Welfare. The Bureau of Statistics in the Ministry of Internal Affairs and Communications has published the Establishment and Enterprise Census. Based on this statistical data, we estimated the minimal necessary number of dedicated industrial physicians in Japan. There are 1,228 workplaces where 1,000 workers or more are regularly employed. Considering that the number of hazardous workplaces where 500-999 workers are regularly employed is around 1,500, it is estimated that at least 2,000-2,500 dedicated industrial physicians are required in Japan.

Application of tryptophan fluorescence to assess sensitizing potentials of chemicals.

There are too many chemical substances around our living space. However, the toxicity of most of them has not been reported, especially regarding their sensitizing potentials. We aimed to develop a simple in vitro method to quantitatively predict the sensitizing potentials of chemicals by measuring the fluorescence of chemical-human serum albumin (HSA) complexes. HSA was treated with test chemicals and then analyzed by tryptophan fluorescence and protein concentration measurement. Four commonly designated sensitizers, two possible sensitizers, and two nonsensitizers were examined using the tryptophan fluorescence assay. HSA fluorescence at 280 nm excitation and 340 nm emission was reduced by toluene 2,4-diisocyanate (TDI), dose dependently. The addition of TDI immediately reduced the fluorescence, and it was stable for 6 h to 21 days after treatment, with a slight decrease. The reduction of HSA fluorescence by chemicals was in the order: commonly designated sensitizers > possible sensitizers > nonsensitizers. Chemical treatment at 0.05 and 0.5 mM led to optimal separation among the three groups. o-Phthalaldehyde (OPA), which has not been evaluated regarding its sensitization potential by any of the authorized organizations, reduced HSA fluorescence as much as the commonly designated sensitizer at final concentrations of the chemical of 0.05 and 0.5 mM. According to our method, OPA is evaluated as a commonly designated sensitizer. The treatment of all test chemicals did not lead to marked differences in the total protein concentrations by either the Lowry or the Bradford method. The assay utilizing tryptophan fluorescence loss of HSA after chemical treatment is a promising method to evaluate the sensitizing potentials of chemicals.

Characteristics of aldehyde dehydrogenase 2 (Aldh2) knockout mice.

Acetaldehyde is an intermediate of ethanol oxidation. It covalently binds to DNA, and is known as a carcinogen. Aldehyde dehydrogenase 2 (ALDH2) is an important enzyme that oxidizes acetaldehyde. Approximately 45% of Chinese and Japanese individuals have the inactive ALDH2 genotypes (ALDH2*2/*2 and ALDH2*1/*2), and Aldh2 knockout mice appear to be a valid animal model for humans with inactive ALDH2. This review gives an overview of published studies on Aldh2 knockout mice, which were treated with ethanol or acetaldehyde. According to these studies, it was found that Aldh2 -/- mice (Aldh2 knockout mice) are more susceptible to ethanol and acetaldehyde-induced toxicity than Aldh2 +/+ mice (wild type mice). When mice were fed with ethanol, the mortality was increased. When they were exposed to atmospheres containing acetaldehyde, the Aldh2 -/- mice showed more severe toxic symptoms, like weight loss and higher blood acetaldehyde levels, as compared with the Aldh2 +/+ mice. Thus, ethanol and acetaldehyde treatment affects Aldh2 knockout mice more than wild type mice. Based on these findings, it is suggested that ethanol consumption and acetaldehyde inhalation are inferred to pose a higher risk to ALDH2-inactive humans. These results also support that ALDH2-deficient humans who habitually consume alcohol have a higher rate of cancer than humans with functional ALDH2.

[Changes of working responsibilities and intentions of industrial physicians who are graduates of University of Occupational and Environmental Health, Japan, in 2001 and 2008 questionnaire analyses].

To investigate the working responsibilities and intentions of industrial physicians who are graduates of University of Occupational and Environmental Health, Japan (UOEH), we performed a questionnaire survey in 2008 and compared the results with those of 2001. To industrial physicians belonging to a company or occupational health organization, we dispatched a questionnaire and asked them to return it with an answer. The items to investigate included their careers and working activities and their intentions to their responsibilities. We obtained the following results. 1. The dissatisfaction with salary and official position was mostly reduced to 24.7% from 29.2% and 19.7% from 29.9%. 2. The practical duty of medical examination of workers and the subsequent management was decreased to 51.5% from 74.7%, while mental health support and the advice on severe health issues such as excess work death were increased to 85.6% from 54.5% and 32.4% from 22.1%. 3. Concerning the working status of industrial physicians, the ratio of the answer of "The industrial physician duties are not positively evaluated by his or her company" was decreased to 23.1% from 32.5%. The investigation of 2008 revealed that the situation of UOEH graduated industrial physicians was substantially improved concerning the dissatisfaction with salary and official position, as compared with the study of 7 years before.

Expression of cytochrome P450 in non-small cell lung cancer.

Lung cancer accounts for most of cancer-related deaths in both men and women. Lung cancer is also associated with cigarette smoking that exposes the individual to carcinogenic chemicals. Normally, CYP enzymes (cytochrome P450s) metabolize carcinogens to inactive derivatives, however, occasionally the action of CYP enzymes leads to development of more potent carcinogens. In addition to the metabolism of carcinogenic compounds, CYP enzymes are also involved in the activation and/or inactivation of agents, which are used in the treatment of lung cancer. Therefore, the local level of CYP enzymes in lung cancer and surrounding tissues could be an important determinant in the efficacy of anticancer drugs. Furthermore, the expression of CYP19 (aromatase), estrogen synthesis P450, was found in more than 80 percent of non-small cell lung cancers. Lung cancer was also found to frequently express CYP24A1 that converts 1 alpha, 25-dihydroxyvitamin D3 to its inactive 24-hydroxylated derivatives. The understanding of the local expression of CYP enzymes in tumor tissues is important in the development of better treatment for lung cancer and a standardized treatment, tailor-made, for individual patients.

Methods and rationale for keeping records of hepatitis virus testing in Japanese workplaces.

In Japan, the Ministry of Health, Labour and Welfare issued corporate guidance that employers should recommend their employees to have tests for hepatitis B virus and hepatitis C virus (HV) at least once in their lifetime. However, employers should treat this information as confidential, even though the testing is carried out along with the health examination designated by the Industrial Safety and Health Law. Therefore, the records of HV tests should not be kept by employers, even though records of medical examinations designated by the law must be. This study aimed to clarify the present method for keeping records of HV infection and the rationale in Japanese workplaces. Questionnaires about viral hepatitis were sent to 118 occupational health physicians, and 81 physicians from 100 workplaces responded. The HV test for employees was conducted in 58 workplaces (75.8% of large, 60.4% of bigger medium-sized and 16.7% of smaller medium-sized enterprises). These workplaces were the types of industries where the risk of infecting other persons was low. Subjects of the HV tests were workers who were suspected to have hepatitis virus, and workers who were applicants. Occupational health physicians from most workplaces answered that records of medical examinations designated by law and records of HV tests were not kept separately and shouldn't be. The opinion that the two types of records should not be kept separately appeared to be more from the workplaces where employers or health insurance covered the cost of the HV test. In these cases, the purpose of conducting HV tests at the workplaces was thought to be both promoting welfare of employees and occupational considerations for workers. Occupational health physicians from about 60% of workplaces had misgivings about employees who had hepatitis virus being discriminated against at the workplace if the HV test was included with the required medical examination. Among occupational health physicians from workplaces where occupational health professionals were in charge of the records, there was no standardized rationale for keeping records. However, most workplaces took into consideration the workers' privacy by getting employees' consent before divulging information to their employers. This relied not only on the occupational health professional's or health/safety officer's ethics, but also the necessity of reviewing the purpose and methods of keeping records of HV testing of employees, based on official notices or the Act on the Protection of Personal Information.

Susceptibility to inhalation toxicity of acetaldehyde in Aldh2 knockout mice.

In this study, we evaluated the inhalation toxicity of acetaldehyde in Aldh2 KO (Aldh -/-) mice, using pathological method. Male C57BL/6 (Aldh2 +/+) mice and Aldh -/- mice were exposed to atmospheres containing acetaldehyde at levels of 0, 125, and 500 ppm for 24 h/day during 14 days. Although the average blood acetaldehyde concentration of Aldh -/- mice was higher than that of Aldh2 +/+ mice in the acetaldehyde exposure group, observable effects by the acetaldehyde exposure on the lung and liver were not different between wild type and ALDH2 null mice. In Aldh2 -/- mice, the levels of 1) erosion of respiratory epithelium and the subepithelial hemorrhage in nose, 2) hemorrhage in nasal cavity, 3) degeneration of respiratory epithelium in larynx, pharynx and trachea, and 4) degeneration of dorsal skin were higher compared with Aldh2 +/+ mice, indicating that Aldh2 -/- mice are more acetaldehyde-sensitive than Aldh2 +/+ mice. This is the first example for studying pathological effects of Aldh2 deficiency using Aldh -/- mice exposed to a low level of acetaldehyde.

Increased cytochrome P450 and aryl hydrocarbon receptor in bronchial epithelium of heavy smokers with non-small cell lung carcinoma carries a poor prognosis.

Smoking induces mutations via the formation of DNA-adducts in the bronchial and alveolar epithelium and contributes to the development of lung cancer. Benz(a)pyrene and nitrosamine, typical carcinogens in cigarette smoke, undergo metabolic activation by the phase I enzymes, such as cytochrome P450 (CYP) 1A1, CYP2A6 and CYP2E1. The transcriptional regulation of these phase I enzymes is regulated by arylhydrocarbon receptor (AH-R) which binds many well-known carcinogens. To identify a cause and effect relationship, the expression of cytochrome CYP and AH-R in the bronchial epithelium was correlated with the history of cigarette smoking in patients with non-small cell lung carcinoma (NSCLC). Although CYP3A+ cells were absent in the bronchial epithelium of all patients, there were many CYP2E1+ cells in heavy (>1000 cigarette/day x year) smokers (38.5%). In contra-distinction, there was significantly less number of CYP2E1+ cells in light (less than 1000 cigarette/day x year) smokers (15.6%) or non-smokers (10.0%). Similarly, there were more CYP1A1+ (19.2%) and CYP2A6+ cells in heavy (65.4%) smokers as compared to non-smokers. The number of AH-R+ cells was also significantly higher in cases with p53 mutation (62.5%) than those without (12.2%) mutation. Since in patients with early NSCLC, CYP positivity showed a close correlation with a poor survival (p less than 0.01), expression of CYP in bronchial epithelium has a prognostic potential.

A comparison of covalent binding of ethanol metabolites to DNA according to Aldh2 genotype.

In order to clarify the effects of ALDH2 polymorphism on the carcinogenicity and organ damage caused by ethanol consumption, labeled ethanol was administered to wild-type (C57BL/6, Aldh2+/+) and Aldh2 knock-out (Aldh2-/-) mice, and DNA adduct levels of organs were compared according to Aldh2 genotype. Aldh2-/- mice, which have the same genetic background as C57BL/6 mice except in the Aldh2 gene, were used as a model of lack of ALDH2 activity in humans. The DNA adduct levels in liver, stomach, and kidney and radioactivity in liver, stomach, kidney, and serum were measured by liquid scintillation counting 6, 12, and 24h after administration. Though radioactivity levels in all organs decreased over time, there were no significant differences in radioactivity between Aldh2+/+ and Aldh2-/- mice. On the other hand, the DNA radioactivity in each organ tested differed significantly between Aldh2+/+ and Aldh2-/- mice 24h after administration. These findings show that ethanol consumption affects DNA in Aldh2-/- mice much more strongly than in Aldh2+/+ mice. According to the IARC document, ethanol consumption is carcinogenic to humans (Group 1). Moreover, several studies have shown that ALDH2-deficient humans who habitually consume ethanol have higher rates of cancer than humans with ALDH2. Our results support these findings of epidemiological studies.

Lack of aldehyde dehydrogenase ameliorates oxidative stress induced by single-dose ethanol administration in mouse liver.

Polymorphism of aldehyde dehydrogenase 2 (ALDH2), denoted ALDH2*2, is far more common in East Asian countries. Acetaldehyde, an intermediate metabolite of ethanol, is metabolized very slowly in people who have ALDH2*2, as the mutated ALDH2 lacks acetaldehyde metabolizing activity. On the other hand, it is well established that metabolism of ethanol causes oxidative stress in liver tissue. To examine the consequences of this polymorphism on ethanol-induced oxidative stress in liver tissue, we conducted a study using Aldh2 knockout mice. Aldh2+/+ and Aldh2-/- mice were orally administered ethanol at a dose of 5g/kg body weight. Levels of malondialdehyde, an indicator of oxidative stress, and glutathione, a key antioxidant, in liver tissue were analyzed 0-24h after administration. Levels of malondialdehyde were significantly lower in Aldh2-/- mice than in Aldh2+/+ mice at 12h after injection, while levels of glutathione were higher in Aldh2-/- mice than in Aldh2+/+ mice at 6 and 12h after injection. Our results suggest that a lack of ALDH ameliorates ethanol-induced oxidative stress in liver tissue.

Single-dose ethanol administration downregulates expression of cytochrome p450 2E1 mRNA in aldehyde dehydrogenase 2 knockout mice.

The polymorphism of aldehyde dehydrogenase 2 (ALDH2), denoted ALDH2*2, is very common in East Asian origin. Acetaldehyde, an intermediate metabolite of ethanol, is metabolized very slowly in people with ALDH2*2 because the mutant ALDH2 protein lacks the activity of acetaldehyde metabolism. On the other hand, it is well established that one of the cytochrome P450 enzymes, CYP2E1, is an activator of carcinogens (e.g., nitorosamines) and a generator of oxidative stress, and it is shown that CYP2E1 was induced by ethanol via gene transcriptional regulation. In the present study, to examine the consequences of ALDH2 polymorphism on transcriptional regulation of CYP2E1 in liver tissue, Aldh2+/+ and Aldh2-/- mice were orally administered 5 g/kg body weight of ethanol and the levels of CYP2E1 mRNA in liver tissue then analyzed. The level of CYP2E1 mRNA 12h after the ethanol administration tended to be higher than the 0-h group in Aldh2+/+ mice, however, it was significantly lower than the 0-h group in Aldh2-/- mice. These findings suggest that single-dose ethanol administration downregulates the expression of cytochrome p450 2E1 mRNA in the presence of inactive ALDH2.

Effects of lifestyle on urinary 1-hydroxypyrene concentration.

This study aimed to clarify the variation of urinary excretion of 1-hydroxypyrene, which is a major metabolite of pyrene, in relation to lifestyle, including factors such as diet and smoking. The study subjects were 251 workers (male: 196, female: 55, mean age: 44.3) who were not occupationally exposed to PAHs. Urine specimens were collected from 8:00 a.m. to 11:00 a.m. and their 1-hydroxypyrene concentrations were determined by HPLC. A questionnaire was distributed in order to learn gross aspects of the subjects' lifestyles, i.e., smoking, alcohol consumption, coffee/black tea intake, and dietary habits. Multiple linear regression analysis revealed that cigarette consumption most strongly affected the 1-hydroxypyrene level in urine, followed by dietary balance. The urinary 1-hydroxypyrene concentrations of smokers were about 2 times higher than those of non-smokers. Subjects who ate more meat and/or fish excreted 1.5-2 times more 1-hydroxypyrene in urine than those who ate more vegetables.