Effects of lifestyle on micronuclei frequency in human lymphocytes in Japanese hard-metal workers.

OBJECTIVE The risks of cardiovascular disease, cancer, and other major causes of mortality are largely attributable to lifestyle factors such as smoking, alcohol drinking, hours of working and sleeping, physical activity, diet, and stress. Earlier studies have suggested that an unhealthy lifestyle is also associated with increased lymphocyte sensitivity to mutagens, oxidative DNA damage level, and leukocyte DNA damage. In order to explore the genotoxicity of unhealthy lifestyle, we evaluated the effect of overall lifestyle as well as some individual lifestyle factors on micronuclei (MN) frequency in cultured human lymphocytes. METHOD The study was conducted among 208 healthy adult (19 to 59 years) male Japanese hard-metal workers. The subjects were divided into groups according to their self-reported good, moderate, and poor lifestyles based on their responses to a questionnaire regarding eight health practices (cigarette smoking, alcohol consumption, sleeping hours, working hours, physical exercise, eating breakfast, balanced nutrition, and mental stress), the presence or absence of each of which was summed to obtain a health practice index (HPI: range 0-8). Peripheral blood was taken and the cytokinesis-block micronuclei (CBMN) assay was performed. RESULTS Total lifestyle quality as measured by the HPI was strongly negatively associated with MN frequency in cultured human lymphocytes (p<0.01). Nutritional imbalance, lack of regular exercise (<2 times per week), insufficient sleep (< or =6 h per day), and overtime working (> or =9 h per day) each contributed significantly to higher MN frequency (all p<0.05). In the smoker group, a significantly higher MN frequency was only found in heavy smokers (p<0.05). On the other hand, mental stress, eating breakfast, and alcohol drinking had no effect on MN frequency. CONCLUSIONS Taken together, these findings indicate that poor lifestyle habits significantly increase MN frequency in human lymphocytes.

[1]  Walter C Willett,et al.  Balancing Life-Style and Genomics Research for Disease Prevention , 2002, Science.

[2]  Martin M. Schumacher,et al.  Use of the alkaline in vivo Comet assay for mechanistic genotoxicity investigations. , 2004, Mutagenesis.

[3]  K. Tamae,et al.  Occupational and lifestyle factors and urinary 8‐hydroxydeoxyguanosine , 2005, Cancer science.

[4]  T. Shirakawa,et al.  Lifestyle effect on total IgE , 1991, Allergy.

[5]  L. Padua,et al.  Influence of glutathione S-transferase polymorphisms on genotoxic effects induced by tobacco smoke. , 2007, Mutation research.

[6]  B W Glickman,et al.  Human micronucleus counts are correlated with age, smoking, and cesium-137 dose in the Goiânia (Brazil) radiological accident. , 1994, Mutation research.

[7]  M. Fenech,et al.  An increased micronucleus frequency in peripheral blood lymphocytes predicts the risk of cancer in humans. , 2006, Carcinogenesis.

[8]  Tatsuya Takeshita,et al.  Chromosome alterations in peripheral lymphocytes as indices of lifestyle and genotoxicity , 1993, International archives of occupational and environmental health.

[9]  M. Fenech,et al.  HUMN project: detailed description of the scoring criteria for the cytokinesis-block micronucleus assay using isolated human lymphocyte cultures. , 2003, Mutation research.

[10]  D. Trichopoulos.  Life-Style and Mortality. A Large-Scale Census-Based Cohort Study in Japan , 1991 .

[11]  M. Fenech,et al.  Effect of smoking habit on the frequency of micronuclei in human lymphocytes: results from the Human MicroNucleus project. , 2003, Mutation research.

[12]  G. Davey Smith,et al.  The role of self-reported stress in the development of breast cancer and prostate cancer: a prospective cohort study of employed males and females with 30 years of follow-up. , 2007, European journal of cancer.

[13]  P. A. van den Brandt,et al.  Cigarette smoking and KRAS oncogene mutations in sporadic colorectal cancer: results from the Netherlands Cohort Study. , 2008, Mutation research.

[14]  T Takeshita,et al.  Healthy lifestyles are associated with higher lymphokine-activated killer cell activity. , 1996, Preventive medicine.

[15]  S. Bonassi,et al.  Influence of sex on cytogenetic end points: evidence from a large human sample and review of the literature. , 1995, Cancer Epidemiology, Biomarkers and Prevention.

[16]  M. Fenech,et al.  The HUman MicroNucleus Project--An international collaborative study on the use of the micronucleus technique for measuring DNA damage in humans. , 1999, Mutation research.

[17]  S. Hodge,et al.  Increased peripheral blood T‐cell apoptosis and decreased Bcl‐2 in chronic obstructive pulmonary disease , 2005, Immunology and cell biology.

[18]  T. Takeshita,et al.  Urinary mutagens and lifestyle factors. , 1996, Preventive Medicine.

[19]  Renato Minozzo,et al.  Micronuclei in peripheral blood lymphocytes of workers exposed to lead. , 2004, Mutation research.

[20]  C. Mascie-Taylor,et al.  The Burden of Chronic Disease , 2003, Science.

[21]  R. Anzion,et al.  Urinary cyclophosphamide excretion and micronuclei frequencies in peripheral lymphocytes and in exfoliated buccal epithelial cells of nurses handling antineoplastics. , 1999, Mutation research.

[22]  A. Krensky,et al.  Healthy lifestyles are associated with higher levels of perforin, granulysin and granzymes A/B-expressing cells in peripheral blood lymphocytes. , 2007, Preventive medicine.

[23]  S. Masetti,et al.  Interactive effect of the glutathione S-transferase genes and cigarette smoking on occurrence and severity of coronary artery risk , 2003, Journal of Molecular Medicine.

[24]  M. Kawano,et al.  Effects of ALDH2 gene polymorphisms and alcohol-drinking behavior on micronuclei frequency in non-smokers. , 2003, Mutation research.

[25]  Hui-Hsuan Lin,et al.  Immunohistochemical Detection of Apoptotic Proteins, p53/Bax and JNK/FasL Cascade, in the Lung of Rats Exposed to Cigarette Smoke , 2006, Archives of Toxicology.

[26]  M. Fenech,et al.  Inclusion of micronuclei in non-divided mononuclear lymphocytes and necrosis/apoptosis may provide a more comprehensive cytokinesis block micronucleus assay for biomonitoring purposes. , 2001, Mutagenesis.

[27]  Y. Takeba,et al.  Effects of cigarette smoking on Fas/Fas ligand expression of human lymphocytes. , 1999, Cellular immunology.

[28]  M. Andreassi,et al.  Genetic Instability, DNA Damage and Atherosclerosis , 2003, Cell cycle.

[29]  G. Fruhmann,et al.  The genotoxic risk of hospital, pharmacy and medical personnel occupationally exposed to cytostatic drugs--evaluation by the micronucleus assay. , 2001, Mutation research.

[30]  Hidetaka Yamamoto,et al.  Genotoxic effects of alcohol in human peripheral lymphocytes modulated by ADH1B and ALDH2 gene polymorphisms. , 2007, Mutation research.

[31]  L. Breslow,et al.  Persistence of health habits and their relationship to mortality. , 1980, Preventive medicine.

[32]  K. Morimoto,et al.  Healthy lifestyles are associated with higher natural killer cell activity. , 1992, Preventive medicine.

[33]  K. Morimoto,et al.  Health practices and leukocyte DNA damage in Japanese hard-metal workers. , 2006, Preventive medicine.

[34]  Stefano Bonassi,et al.  Low intake of calcium, folate, nicotinic acid, vitamin E, retinol, beta-carotene and high intake of pantothenic acid, biotin and riboflavin are significantly associated with increased genome instability--results from a dietary intake and micronucleus index survey in South Australia. , 2005, Carcinogenesis.

[35]  G. Guanti,et al.  Sister chromatid exchange (SCE) and micronucleus (MN) frequencies in lymphocytes of gasoline station attendants. , 1998, Mutation research.

[36]  M. Fenech.  Cytokinesis-block micronucleus cytome assay , 2007, Nature Protocols.

[37]  G. Duménil,et al.  The micronucleus assay in human lymphocytes: screening for inter-individual variability and application to biomonitoring. , 1994, Carcinogenesis.

[38]  H. Norppa,et al.  Chromosomal aberrations in lymphocytes predict human cancer independently of exposure to carcinogens. European Study Group on Cytogenetic Biomarkers and Health. , 2000, Cancer research.

[39]  F. Mitelman,et al.  Sister chromatid exchanges and structural chromosome aberrations in relation to age and sex , 2004, Human Genetics.

[40]  R. Klein,et al.  Relation of smoking to the incidence of age-related maculopathy. The Beaver Dam Eye Study. , 1998, American journal of epidemiology.

[41]  J. Marrero,et al.  Alcohol, tobacco and obesity are synergistic risk factors for hepatocellular carcinoma. , 2005, Journal of hepatology.

[42]  C. la Vecchia,et al.  Smoking cessation and the risk of oesophageal cancer: An overview of published studies. , 2006, Oral oncology.

[43]  W H Dietz,et al.  The continuing epidemic of obesity in the United States. , 2000, JAMA.

[44]  M. Dusinska,et al.  The relationship between micronuclei in human lymphocytes and selected micronutrients in vegetarians and non-vegetarians. , 2006, Mutation research.

[45]  M. Fenech,et al.  The Effects of GSTM1 and GSTT1 Polymorphisms on Micronucleus Frequencies in Human Lymphocytes In vivo , 2006, Cancer Epidemiology Biomarkers & Prevention.

[46]  C. Bolognesi,et al.  Cytogenetic biomonitoring in traffic police workers: Micronucleus test in peripheral blood lymphocytes , 1997, Environmental and molecular mutagenesis.

[47]  W. Chang,et al.  Cytogenetic effect of chronic low-dose, low-dose-rate γ-radiation in residents of irradiated buildings , 1997, The Lancet.

[48]  M. Fenech,et al.  HUman MicroNucleus project: international database comparison for results with the cytokinesis‐block micronucleus assay in human lymphocytes: I. Effect of laboratory protocol, scoring criteria, and host factors on the frequency of micronuclei , 2001, Environmental and molecular mutagenesis.

[49]  M D Shelby,et al.  Chromosomal aberration and sister-chromatid exchange frequencies in peripheral blood lymphocytes of a large human population sample. , 1988, Mutation research.

[50]  H. Norppa,et al.  Chromosomal aberrations in lymphocytes predict human cancer: a report from the European Study Group on Cytogenetic Biomarkers and Health (ESCH). , 1998, Cancer research.

[51]  M. Kirsch‐Volders,et al.  Absence of significant genotoxicity in lymphocytes and urine from workers exposed to moderate levels of cobalt‐containing dust: A cross‐sectional study , 2000, Environmental and molecular mutagenesis.

[52]  Jeffrey V. Johnson,et al.  Long working hours, occupational health and the changing nature of work organization. , 2006, American journal of industrial medicine.

[53]  M. Witt,et al.  Manifestations of ageing at the cytogenetic level. , 2003, Journal of applied genetics.

[54]  K. Morimoto,et al.  Personal health practices and attitudes toward nonsmokers' legal rights in Japan. , 1991, Social science & medicine.

[55]  T. Takeuchi,et al.  A comparison of the 8-hydroxydeoxyguanosine, chromosome aberrations and micronucleus techniques for the assessment of the genotoxicity of mercury compounds in human blood lymphocytes. , 1996, Mutation research.

[56]  J. Prignot.  Quantification and chemical markers of tobacco-exposure. , 1987, European journal of respiratory diseases.

[57]  J. Yager,et al.  Biological and environmental monitoring of occupational exposure to cyclophosphamide in industry and hospitals. , 1988, Mutation research.

[58]  T. Takeshita,et al.  Lifestyles and mental health status are associated with natural killer cell and lymphokine-activated killer cell activities. , 2001, The Science of the total environment.

[59]  R. Preston,et al.  Chromosome aberrations, micronuclei, aneuploidy, sister chromatid exchanges, and cancer risk assessment. , 1996, Mutation research.

[60]  M. Fenech.  In vitro micronucleus technique to predict chemosensitivity. , 2005, Methods in molecular medicine.

[61]  P. H. Saldanha,et al.  Micronucleus investigation of alcoholic patients with oral carcinomas. , 2002, Genetics and molecular research : GMR.