Skip to main content

Advertisement

Log in

Evidence of genotoxicity in lymphocytes of non-smoking alcoholics

  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

Alcohol abuse is a significant public health issue. Epidemiological studies conducted on different populations consistently showed that consumption of alcoholic beverages is associated with cytogenetic damages and higher risk for several types of cancer. However, the interpretation of many cytogenetic studies resulted complicated because some confounding factors, such as smoking habit, are not always taken into account. In the present study, the frequency of sister chromatid exchanges (SCEs), chromosome aberrations (CAs) and micronuclei (MNs) in cultured human lymphocytes was assessed on 15 alcoholic and 15 non-alcoholic control male subjects. Moreover, considering the implication of the Glutathione S-transferases gene polymorphisms in the genetic susceptibility to alcoholic liver diseases, we considered an important issue to evaluate the relationship between these gene polymorphisms and the cytogenetic damage. In our sample we exclusively considered individuals that did not smoke nor consume drugs for a period of at least 2 years prior to the analysis. Statistically significant differences were found between alcoholics and controls in the frequency of SCEs/cell (P = 0.001), RI value (P = 0.001), CAs (P = 0.002) and CAB (P = 0.002). Vice versa, no significant differences were found between alcoholics and controls in terms of MNs frequency and CBPI value. In both samples, no statistically significant association was found between the analysed GSTs gene polymorphisms and the frequencies of MNs, SCEs and CAs. Finally, among alcoholics we found a positive correlation between SCEs and CAs frequencies and the duration of alcohol abuse.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Adler RA (1992) Clinical review 33: clinically important effects of alcohol on endocrine function. J Clin Endocrinol Metab 74:957–960

    CAS  PubMed  Google Scholar 

  2. Barnett YA, King CM (1995) An investigation of antioxidants status, DNA repair capacity and mutation as a function of age in humans. Mutat Res 338:115–128

    Article  CAS  PubMed  Google Scholar 

  3. Bolognesi C, Abbondandolo A, Barale R et al (1997) Age-related increase of baseline frequencies of sister chromatid exchanges, chromosome aberrations, and micronuclei in human lymphocytes. Cancer Epidemiol Biomark Prev 6(4):249–256

    CAS  Google Scholar 

  4. Bonassi S, Hagmar L, Strömberg U et al (2000) Chromosomal aberrations in lymphocytes predict human cancer independently of exposure to carcinogens. Cancer Res 60:1619–1625

    CAS  PubMed  Google Scholar 

  5. Bonassi S, Znaor A, Norppa H, Hagmar L (2004) Chromosomal aberrations and risk of cancer in humans: an epidemiologic perspective. Cytogenet Genome Res 104:376–382

    Article  CAS  PubMed  Google Scholar 

  6. Burim RV, Canalle R, Takahashi CS et al (2004) Clastogenic effect of ethanol in chronic and abstinent alcoholics. Mutat Res 560(2):187–198

    Article  CAS  PubMed  Google Scholar 

  7. Butler MG, Sanger WG, Veonett GE (1981) Increased frequency of sister-chromatid exchanges in alcoholics. Mutat Res 85(2):71–76

    Article  CAS  PubMed  Google Scholar 

  8. Castelli E, Hrelia P, Maffei F, Fimognari C, Foschi FG, Caputo F, Cantelli-Forti G, Stefanini GF, Gasbarrini G (1999) Indicators of genetic damage in alcoholics: reversibility after alcohol abstinence. Hepatogastroenterology 46(27):1664–1668

    CAS  PubMed  Google Scholar 

  9. Crebelli R, Conti G, Conti L, Carere A (1989) A comparative study on ethanol and acetaldehyde as inducers of chromosome malsegregation in Aspergillus nidulans. Mutat Res 215:187–195

    Article  CAS  PubMed  Google Scholar 

  10. Demirhan O, Tastemir D (2008) Cytogenetic effects of ethanol on chronic alcohol users. Alcohol Alcohol 43(2):127–136

    Article  CAS  PubMed  Google Scholar 

  11. Du X, Squier CA, Kremer MJ, Wertz PW (2000) Penetration of N-nitrosonornicotine (NNN) across oral mucosa in the presence of ethanol and nicotine. J Oral Pathol Med 29:80–85

    Article  CAS  PubMed  Google Scholar 

  12. Elhajouji A, Cunha M, Kirsch-Volders M (1998) Spindle poisons can induce polyploidy by mitotic slippage and micronucleate mononucleates in the cytokinesis-block assay. Mutagenesis 13:193–198

    Article  CAS  PubMed  Google Scholar 

  13. Fenech M (1998) Important variables that influence base-line micronucleus frequency in cytokinesis-blocked lymphocytes as biomarker for DNA damage in human populations. Mutat Res 404:155–165

    Article  CAS  PubMed  Google Scholar 

  14. Fenech M (2000) The in vitro micronucleus technique. Mutat Res 455:81–95

    Article  CAS  PubMed  Google Scholar 

  15. Fenech M, Chang WP, Kirsch-Volders M, Holland N, Bonassi S, Zeiger E (2003) Human Micron Nucleus project (HUMN project): detailed description of the scoring criteria for the cytokinesis-block micronucleus assay using isolated human lymphocyte cultures. Mutat Res 534(1–2):65–75

    Article  CAS  PubMed  Google Scholar 

  16. Garcia-Sagredo JM (2008) Fifty years of cytogenetics: a parallel view of the evolution of cytogenetics and genotoxicology. Biochim Biophys Acta 1779(6–7):363–375

    Article  CAS  PubMed  Google Scholar 

  17. Gattás GJ, Saldanha PH (1997) Chromosomal aberrations in peripheral lymphocytes of abstinent alcoholics. Alcohol Clin Exp Res 21:238–243

    Article  PubMed  Google Scholar 

  18. Hagmar L, Bonassi S, Stromberg U, Brogger A, Knudsen LE, Norppa H, Reuterwall C (1998) Chromosomal aberrations in lymphocytes predict human cancer: a report from the European study group on cytogenetic biomarkers and health (ESCH). Cancer Res 58:4117–4121

    CAS  PubMed  Google Scholar 

  19. Iarmarcovai G, Bonassi S, Sari-Minodier I, Baciuchka-Palmaro M, Botta A, Orsìere T (2007) Exposure to genotoxic agents, host factors, and lifestyle influence the number of centromeric signals in micronuclei: a pooled re-analysis. Mutat Res 615:18–27

    Article  CAS  PubMed  Google Scholar 

  20. IARC (1988) Alcohol drinking. international agency for research on cancer. Monographs on the evaluation of carcinogenic risk to human, vol 54. International Agency for Research on Cancer, Lyon, pp 251–321

    Google Scholar 

  21. IARC (2010) Alcohol consumption and Ethyl Carbamate. Monographs on the evaluation of carcinogenic risk to human, vol 96. International Agency for Research on Cancer, Lyon, pp 173–1001

    Google Scholar 

  22. Inoue M, Tajima K, Hirose K, Kuroishi T, Gao CM, Kitoh T (1994) Life-style and subsite of gastric cancer-joint effect of smoking and drinking habits. Int J Cancer 56:494–499

    Article  CAS  PubMed  Google Scholar 

  23. Kafer E (1984) Disruptive effects of ethyl alcohol on mitotic chromosomes segregation in diploid and haploid strains of Aspergillus nidulans. Mutat Res 135:53–75

    Article  CAS  PubMed  Google Scholar 

  24. Karaoğuz MY, Coşar B, Arikan Z, Başaran F, Menevşe A, Menevşe S (2005) Increased frequency of sister chromatid exchanges in peripheral lymphocytes of alcoholics and cigarette smokers. Cell Biol Int 29(2):165–168

    Article  PubMed  Google Scholar 

  25. Kaufman MH (1983) Ethanol-induced chromosomal abnormalities at conception. Nature 302:258–260

    Article  CAS  PubMed  Google Scholar 

  26. Kaufman MH (1985) An hypothesis regarding the origin of aneuploidy in man: indirect evidence from an experimental model. J Med Genet 22:171–178

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  27. Kaufman MH (1997) The teratogenic effects of alcohol following exposure during pregnancy, and its influence on the chromosome constitution of the pre-ovulatory egg. Alcohol Alcohol 32:113–128

    Article  CAS  PubMed  Google Scholar 

  28. Kaufman MH, Bain IM (1984) Influence of ethanol on chromosome segregation during the first and second meiotic divisions in the mouse egg. J Exp Zool 230:315–320

    Article  CAS  PubMed  Google Scholar 

  29. Lazutka JR, Dedonyte V, Lekevicius RK (1992) Sister chromatid exchanges in lymphocytes of normal and alcoholic subjects. Experientia 48(5):508–512

    Article  CAS  PubMed  Google Scholar 

  30. Lee KW, Kuo WR, Tsai SM et al (2005) Different impact from betel quid, alcohol and cigarette: risk factors for pharyngeal and laryngeal cancer. Int J Cancer 117:831–836

    Article  CAS  PubMed  Google Scholar 

  31. Lieber CS (1994) Alcohol and the liver: update. Gastroenterology 106:1085–1105

    CAS  PubMed  Google Scholar 

  32. Maffei F, Fimognari C, Castelli E, Stefanini GF, Forti GC, Hrelia P (2000) Increased cytogenetic damage detected by FISH analysis on micronuclei in peripheral lymphocytes from alcoholics. Mutagenesis 15(6):517–523

    Article  CAS  PubMed  Google Scholar 

  33. Mandayam S, Jamal MM, Morgan TR (2004) Epidemiology of alcoholic liver disease. Semin Liver Dis 24:217–232

    Article  PubMed  Google Scholar 

  34. Marcos M, Pastor I, Chamorro AJ, Ciria-Abad S, Gonzalez-Sarmiento R, Laso FJ (2011) Meta-analysis: glutathione-S-transferase allelic variants are associated with alcoholic liver disease. Aliment Pharmacol Ther 34:1159–1172

    Article  CAS  PubMed  Google Scholar 

  35. Nakamura K, Iwalashi K, Itoh M, Ameno K, Ijiri I, Takeuchi Y, Suwaki H (2000) Immunohistochemical study on acetaldehyde adducts in alcohol-fed mice. Alcohol Clin Exp Res 24(4):93S–96S

    CAS  PubMed  Google Scholar 

  36. Nebert DW, McKinnon RA, Puga A (1996) Human drug metabolising enzyme polymorphisms effects on risk of toxicity and cancer DNA. Cell Biol 15:273–280

    CAS  Google Scholar 

  37. Nersesyan A, Muradyan R, Kundi M, Knasmueller S (2011) Impact of smoking on the frequencies of micronuclei and other nuclear abnormalities in exfoliated oral cells: a comparative study with different cigarette types. Mutagenesis 26(2):295–301

    Article  CAS  PubMed  Google Scholar 

  38. Obe G, Anderson D (1987) International commission for protection against environmental mutagens and carcinogens. ICPEMC Working Paper No. 15/1. Genetic effects of ethanol. Mutat Res 186(3):177–200

    Article  CAS  PubMed  Google Scholar 

  39. Parry EM, Parry JM, Corso C et al (2002) Detection and characterization of mechanisms of action of aneugenic chemicals. Mutagenesis 17(6):509–521

    Article  CAS  PubMed  Google Scholar 

  40. Pemble S, Schroeder KR, Spencer SR, Meyer DJ, Hallier E, Bolt HM, Ketterer B, Taylor JB (1994) Human glutathione S-transferase theta (GSTT1): cDNA cloning and the characterization of a genetic polymorphism. Biochem J 300:271–276

    CAS  PubMed Central  PubMed  Google Scholar 

  41. Rey M, Palermo AM, Muñoz ER (1992) Nondisjunction induced by ethanol in Drosophila melanogaster females. Mutat Res 268(1):95–104

    Article  CAS  PubMed  Google Scholar 

  42. Roy B, Majumder PP, Dey B, Chakraborty M, Banerjee S, Roy M, Mukherjee N, Sil SK (2001) Ethnic differences in distributions of GSTM1 and GSTT1 homozygous “Null” genotypes in India. Hum Biol 73(3):443–450

    Article  CAS  PubMed  Google Scholar 

  43. Santovito S, Cervella P, DelPero M (2011) In vitro aneugenic effects of the fungicide thiabendazole evaluated in human lymphocytes by the micronucleus assay. Arch Toxicol 85:689–693

    Article  CAS  PubMed  Google Scholar 

  44. Santovito A, Schilirò T, Castellano S, Cervella P, Bigatti MP, Gilli G, Bono R, DelPero M (2011) Combined analysis of chromosomal aberrations and glutathione S-transferase M1 and T1 polymorphisms in pathologists occupationally exposed to formaldehyde. Arch Toxicol 85:1295–1302

    Article  CAS  PubMed  Google Scholar 

  45. Santovito S, Cervella P, DelPero M (2014) Increased frequency of chromosomal aberrations and sister chromatid exchanges in peripheral lymphocytes of radiology technicians chronically exposed to low levels of ionizing radiations. Environ Toxicol Phar 37:396–403

    Article  CAS  Google Scholar 

  46. Savolainen VT, Pajarinen J, Perola M, Penttila A, Karhunen PJ (1996) Glutathione-S-Transferase GST M1 “Null” genotype and the risk of alcoholic liver disease. Alcohol Clin Exp Res 20(8):1340–1345

    Article  CAS  PubMed  Google Scholar 

  47. Seitz HK, Stickel F (2006) Risk factors and mechanisms of hepatocarcinogenesis with special emphasis on alcohol and oxidative stress. Biol Chem 387(4):349–360

    Article  CAS  PubMed  Google Scholar 

  48. Sierra-Torres MS, Arboleda-Moreno YY, Hoyos LS, Sierra-Torres CH (2004) Chromosome aberrations among cigarette smokers in Colombia. Mutat Res 562(1–2):67–75

    Article  CAS  PubMed  Google Scholar 

  49. Stich HF, Rosin MP (1983) Quantitating the synergistic effect of smoking and alcohol consumption with the micronucleus test on human buccal mucosa cells. Int J Cancer 31(3):305–308

    Article  CAS  PubMed  Google Scholar 

  50. Vioque J, Barber X, Bolumar F, Porta M, Santibáñez M, de la Hera MG, Moreno-Osset E, PANESOES Study Group (2008) Oesophageal cancer risk by type of alcohol drinking and smoking: a case-control study in Spain. BMC Cancer 8(1):221

    Article  PubMed Central  PubMed  Google Scholar 

  51. Walsh P, Metzger DA, Higuchi R (1991) Chelex 100 as a Medium for simple extraction of DNA for PCR-based typing from forensic material. Biotechniques 10:506

    CAS  PubMed  Google Scholar 

  52. Wilson DM 3rd, Thompson LH (2007) Molecular mechanisms of sister-chromatid exchange. Mutat Res 616(1–2):11–23

    Article  CAS  PubMed  Google Scholar 

  53. Zhong S, Wyllie AH, Barnes D, Wolf CR, Spurr NK (1993) Relationship between GSTM1 genetic polymorphism and susceptibility to bladder, breast and colon cancer. Carcinogenesis 14:1821–1824

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by Grants from the Italian Ministry of University and Scientific Research. We are grateful to Natascha Rogge for her valuable help and criticism and to all volunteers who participated in this study.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Alfredo Santovito.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Santovito, A., Cervella, P. & Delpero, M. Evidence of genotoxicity in lymphocytes of non-smoking alcoholics. Mol Biol Rep 42, 53–59 (2015). https://doi.org/10.1007/s11033-014-3739-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-014-3739-8

Keywords

Navigation