Top

Environmental Health and Preventive Medicine

Published in:

01-05-2010 | Regular Article

Effect of gene polymorphisms and ethanol consumption on micronucleus frequency in human reticulocytes: a preliminary study

Authors: Chuancheng Wu, Yuquan Lu, Kanehisa Morimoto

Published in: Environmental Health and Preventive Medicine | Issue 3/2010

Abstract

Objective

Results from previous studies suggest that alcohol consumption can be genotoxic on peripheral lymphocytes. The aim of our study was to examine the association of alcohol consumption and its genotoxic effect on hematopoietic stem cells in vivo.

Methods

We investigated 156 healthy Japanese males in a cross-sectional study. Lifestyles, including alcohol drinking behavior and cigarette smoking status, were investigated by means of a self-completed questionnaire. Polymorphisms of ADH1B and ALDH2 were identified by PCR–restriction fragment length polymorphism (RFLP) analysis. The presence of micronuclei in transferrin-positive reticulocytes (MN-RET) was detected with a single-laser flow cytometer. Associations between the genetic polymorphisms, lifestyle factors, and MN-RET frequency were statistically analyzed.

Results

We found a significant difference in the mean frequencies of MN-RET between habitual drinkers and non-habitual drinkers (P = 0.043), and between the ALDH2*1/*1 and ALDH2*2/*2 genotype (P = 0.015). The ADH1B*2 and ALDH2*2 haplotype was estimated to have a significantly higher influence on MN-RET frequency than the ADH1B*2 and ALDH2*1 haplotype (P = 0.00035), and the frequency of alcohol consumption played a significant role in MN-RET frequency on the background of the ADH1B*2 and ALDH2*1 haplotype (P = 0.012).

Conclusion

The results of our study suggest a possible association between the ADH1B and ALDH2 polymorphism and the genotoxic effects of alcohol drinking on hematopoietic stem cells.

Norppa H. Cytogenetic markers of susceptibility: influence of polymorphic carcinogen-metabolizing enzymes. Environ Health Perspect. 1997;105[Suppl 4]:829–35.CrossRefPubMed

Iarmarcovai G, et al. Micronuclei frequency in peripheral blood lymphocytes of cancer patients: a meta-analysis. Mutat Res. 2008;659(3):274–83.CrossRefPubMed

Goetz R, Sram RJ, Dohnalova J. Relationship between experimental results in mammals and man. I. Cytogenetic analysis of bone marrow injury induced by a single dose of cyclophosphamide. Mutat Res. 1975;31(4):247–54.PubMed

Jensen MK, Nyfors A. Cytogenetic effects of methotrexate on human cells in vivo: comparison between results obtained by chromosome studies on bone-marrow cells and blood lymphocytes and by the micronucleus test. Mutat Res. 1979;64(5):339–43.PubMed

Schlegel R, MacGregor JT, Everson RB. Assessment of cytogenetic damage by quantitation of micronuclei in human peripheral blood erythrocytes. Cancer Res. 1986;46(7):3717–21.PubMed

Abramsson-Zetterberg L, et al. Human cytogenetic biomonitoring using flow-cytometric analysis of micronuclei in transferrin-positive immature peripheral blood reticulocytes. Environ Mol Mutagen. 2000;36(1):22–31.CrossRefPubMed

Abramsson-Zetterberg L, Grawe J, Zetterberg G. The micronucleus test in rat erythrocytes from bone marrow, spleen and peripheral blood: the response to low doses of ionizing radiation, cyclophosphamide and vincristine determined by flow cytometry. Mutat Res. 1999;423(1–2):113–24.PubMed

Badger TM, et al. Alcohol metabolism: role in toxicity and carcinogenesis. Alcohol Clin Exp Res. 2003;27(2):336–47.CrossRefPubMed

Schoedel KA, Tyndale RF. Induction of nicotine-metabolizing CYP2B1 by ethanol and ethanol-metabolizing CYP2E1 by nicotine: summary and implications. Biochim Biophys Acta. 2003;1619(3):283–90.PubMed

10.

Bosron WF, Li TK. Genetic polymorphism of human liver alcohol and aldehyde dehydrogenases, and their relationship to alcohol metabolism and alcoholism. Hepatology. 1986;6(3):502–10.CrossRefPubMed

11.

Bosron WF, Magnes LJ, Li TK. Kinetic and electrophoretic properties of native and recombined isoenzymes of human liver alcohol dehydrogenase. Biochemistry. 1983;22(8):1852–7.CrossRefPubMed

12.

Brennan P, et al. Pooled analysis of alcohol dehydrogenase genotypes and head and neck cancer: a HuGE review. Am J Epidemiol. 2004;159(1):1–16.CrossRefPubMed

13.

Quertemont E. Genetic polymorphism in ethanol metabolism: acetaldehyde contribution to alcohol abuse and alcoholism. Mol Psychiatry. 2004;9(6):570–81.CrossRefPubMed

14.

Crabb DW, et al. Genotypes for aldehyde dehydrogenase deficiency and alcohol sensitivity. The inactive ALDH2(2) allele is dominant. J Clin Invest. 1989;83(1):314–6.CrossRefPubMed

15.

Neumark YD, et al. Alcohol dehydrogenase polymorphisms influence alcohol-elimination rates in a male Jewish population. Alcohol Clin Exp Res. 2004;28(1):10–4.CrossRefPubMed

16.

Offer T, et al. A simple assay for frequency of chromosome breaks and loss (micronuclei) by flow cytometry of human reticulocytes. FASEB J. 2005;19(3):485–7.PubMed

17.

Lee CH, et al. Independent and combined effects of alcohol intake, tobacco smoking and betel quid chewing on the risk of esophageal cancer in Taiwan. Int J Cancer. 2005;113(3):475–82.CrossRefPubMed

18.

Tregouet DA, Garelle V. A new JAVA interface implementation of THESIAS: testing haplotype effects in association studies. Bioinformatics. 2007;23(8):1038–9.CrossRefPubMed

19.

Latvala J, Parkkila S, Niemela O. Excess alcohol consumption is common in patients with cytopenia: studies in blood and bone marrow cells. Alcohol Clin Exp Res. 2004;28(4):619–24.CrossRefPubMed

20.

Wickramasinghe SN, et al. Metabolism of ethanol by human bone marrow cells. Acta Haematol. 1981;66(4):238–43.CrossRefPubMed

21.

Latvala J, et al. Acetaldehyde adducts in blood and bone marrow of patients with ethanol-induced erythrocyte abnormalities. Mol Med. 2001;7(6):401–5.PubMed

22.

Meagher RC, Sieber F, Spivak JL. Suppression of hematopoietic-progenitor-cell proliferation by ethanol and acetaldehyde. N Engl J Med. 1982;307(14):845–9.PubMedCrossRef

23.

Korte A, et al. Influence of chronic ethanol uptake and acute acetaldehyde treatment on the chromosomes of bone-marrow cells and peripheral lymphocytes of Chinese hamsters. Mutat Res. 1981;88(4):389–95.CrossRefPubMed

24.

Barale R, et al. Sister chromatid exchange and micronucleus frequency in human lymphocytes of 1, 650 subjects in an Italian population: II. Contribution of sex, age, and lifestyle. Environ Mol Mutagen. 1998;31(3):228–42.CrossRefPubMed

25.

Fenech M, Rinaldi J. The relationship between micronuclei in human lymphocytes and plasma levels of vitamin C, vitamin E, vitamin B12 and folic acid. Carcinogenesis. 1994;15(7):1405–11.CrossRefPubMed

26.

Au WW, et al. Factors contributing to chromosome damage in lymphocytes of cigarette smokers. Mutat Res. 1991;260(2):137–44.CrossRefPubMed

27.

Tomanin R, et al. Influence of smoking habit on the frequency of micronuclei in human lymphocytes by the cytokinesis block method. Mutagenesis. 1991;6(2):123–6.CrossRefPubMed

28.

Vaglenov A, Karadjo A. Micronucleus frequencies in Bulgarian control populations. Cent Eur J Occup Environ Med. 1997;3:187–94.

29.

Bolognesi C, et al. Cytogenetic biomonitoring in traffic police workers: micronucleus test in peripheral blood lymphocytes. Environ Mol Mutagen. 1997;30(4):396–402.CrossRefPubMed

30.

Bolognesi C, et al. Cytogenetic analysis of a human population occupationally exposed to pesticides. Mutat Res. 1993;285(2):239–49.PubMed

31.

Bukvic N, et al. Sister chromatid exchange (SCE) and micronucleus (MN) frequencies in lymphocytes of gasoline station attendants. Mutat Res. 1998;415(1–2):25–33.PubMed

32.

Singh NP, Khan A. Acetaldehyde: genotoxicity and cytotoxicity in human lymphocytes. Mutat Res. 1995;337(1):9–17.PubMed

33.

Butler MG, Sanger WG, Veonett GE. Increased frequency of sister-chromatid exchanges in alcoholics. Mutat Res. 1981;85(2):71–6.PubMed

34.

Maffei F, et al. Increased cytogenetic damage detected by FISH analysis on micronuclei in peripheral lymphocytes from alcoholics. Mutagenesis. 2000;15(6):517–23.CrossRefPubMed

35.

Morimoto K, Takeshita T. Low Km aldehyde dehydrogenase (ALDH2) polymorphism, alcohol-drinking behavior, and chromosome alterations in peripheral lymphocytes. Environ Health Perspect. 1996;104[Suppl 3]:563–7.CrossRefPubMed

36.

Abramsson-Zetterberg L, Zetterberg G, Grawe J. The time-course of micronucleated polychromatic erythrocytes in mouse bone marrow and peripheral blood. Mutat Res. 1996;350(2):349–58.PubMed

Title: Effect of gene polymorphisms and ethanol consumption on micronucleus frequency in human reticulocytes: a preliminary study
Authors: Chuancheng Wu
Yuquan Lu
Kanehisa Morimoto
Publication date: 01-05-2010
Publisher: Springer Japan
Published in: Environmental Health and Preventive Medicine / Issue 3/2010
Print ISSN: 1342-078X
Electronic ISSN: 1347-4715
DOI: https://doi.org/10.1007/s12199-009-0126-5

2024 ASCO Annual Meeting

Springer Medicine

Effect of gene polymorphisms and ethanol consumption on micronucleus frequency in human reticulocytes: a preliminary study

Abstract

Objective

Methods

Results

Conclusion

2024 ASCO Annual Meeting

Springer Medicine

Abstract

Objective

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 3/2010

Bone fracture in physically disabled children attending schools for handicapped children in Japan

Changes in thioredoxin concentrations: an observation in an ultra-marathon race

History of blood transfusion before 1990 is associated with increased risk for cancer mortality independently of liver disease: a prospective long-term follow-up study

Assessment of intervention strategies against a novel influenza epidemic using an individual-based model

Examination of useful items for the assessment of fall risk in the community-dwelling elderly Japanese population

Abstracts from Nippon Eiseigaku Zasshi (Japanese Journal of Hygiene) vol. 65 no. 1