Formation of DNA crosslinks in human lymphocytes by acetaldehyde revealed by the comet assay

• Autorzy: Blasiak J. , Gloc-Fudala E. , Trzeciak A.
• Języki publikacji: EN

Abstrakty

EN

Ethyl alcohol can be mutagenic, cancerogenic and teratogenic in man and its mutagenicity can be attributed to its first and major metabolite, acetaldehyde, which was reported to form adducts with DNA and proteins and DNA strand breaks. It was suggested that DNA crosslinks can be predominant DNA adducts of acetaldehyde but these results were obtained with the alkaline elution technique which provides no information on the extent of DNA damage at individual cell level. The comet assay is a technique, which allows detecting double- and single-strand DNA breaks caused by a broad spectrum of mutagens. It is also a suitable tool for the detection of crosslinking agents. Human peripheral blood lymphocytes were incubated for 1 h at 37°C with 3, 10, 30 and 100 mM of acetaldehyde. The alkaline comet assay was used to assess DNA damage. A dose-dependent decrease in the migration of DNA of acetaldehyde-treated cells was observed. Similar results were obtained when a recognized DNA crosslinking agent, formaldehyde was used. The results obtained suggest that acetaldehyde may form crosslinks with DNA in human lymphocytes. The nature of the crosslinks remains unknown and needs further investigations.

Słowa kluczowe

EN

DNA cross; man; acetaldehyde genotoxicity; lymphocyte; formaldehyde; DNA damage; ethanol metabolism

• Wydawca: -
• Czasopismo: Cellular and Molecular Biology Letters
• Rocznik: 1999
• Tom: 04
• Numer: 2
• Opis fizyczny: p.181-187,fig.

Twórcy

autor

Blasiak J.

• University of Lodz, Banacha 12-16, 90-237 Lodz, Poland

autor

Gloc-Fudala E.

autor

Trzeciak A.

Bibliografia

• 1. Casini, A., Pellegrini, G., Ceni, E., Salzano, R., Parola, M., Robino, G., Milani, S., Dianzani, M. U., Surrenti, C. Human hepatic stellate cells express class I alcohol dehydrogenase and aldehyde dehydrogenase but not cytochrome P4502E1. J. Hepatol. 28 (1998) 40-45.
• 2. Pikkerainen, P. H., Baraone, E., Jauhonen, P., Seitz, H. K., Lieber, C. S. Contribution of oropharynx microflora and of lung microsomes to acetaldehyde in expired air after alcohol ingestion. J. Lab. Clin. Med. 97 (1981) 631-636.
• 3. Murata, M., Takayama, K., Choi, B. C., Pak, A. W. A nested-case control study on alcohol drinking, tobacco smoking, and cancer. Cancer Detect. Prev. 20 (1996) 557-565.
• 4. Franceschi, S., Talamini, R., Barra, S., Baron, A. E., Negri, E., Bidoli, E. Smoking and drinking in relation to cancers of the oral cavity, pharynx, larynx and esophagus in northern Italy. Cancer Res. 50 (1990) 6502-6507.
• 5. Frankel-Conrat, H. and Singer, B. Nucleoside adducts are formed by cooperative reaction of acetaldehyde and alcohols: possible mechanism for the role of ethanol in carcinogenesis. Proc. Natl. Acad. Sci. USA 85 (1988) 3758-3761.
• 6. Vaca, C., Fahg, J. L., Schweda, E. Studies of the reaction of acetaldehyde with deoxynucleotides. Chem. Biol. Interact. 98 (1995) 51-67.
• 7. Baraona, E., Liu, W., Ma, X., Svegliati-Baroni, G., Leiber, C. S. Acetaldehyd—collagen adducts in N-nitrosodimethylamine-induced liver cirrhosis in rats. Life. Sci. 52 (1993) 1249-1255.
• 8. Kuykendall, J. R. and Bogdanfy, M. S. Reaction kinetics of DNA-histone crosslinking by vinyl acetate and acetaldehyde. Carcinogenesis 13 (1992) 2095-2100.
• 9. Singh, N. P. and Khan, A. Acetaldehyde: genotoxicity and cytotoxicity in human lymphocytes. Mutation Res. 337 (1995) 9-17.
• 10. Lambert, B., Chen, Y., He, S. M., Sten, M. DNA cross-links in human leukocytes treated with vinyl acetate and acetaldehyde in vitro. Mutat Res. 146 (1985) 301-303.
• 11. Matsuda, T., Kawanishi, M., Yagi, T., Matsui, S., Takebe, H. Specific tandem GG to TT base substitutions induced by acetaldehyde are due to intra-strand crosslinks between adjacent guanine bases. Nucleic Acids Res. 26 (1998) 1769-1774.
• 12. Singh, N. P., Stephens, R. E., Schneider, E. L. Modification of alkaline microgel electrophoresis for sensitive detection of DNA damage. Int. J. Radiat. Biol. 66 (1994) 23-28.
• 13. Ashby, J., Tinwell, H., Lefevre, P. A., Browne, M. A. The single cell gel electrophoresis assay for induced DNA damage (comet assay): measurement of tail length and moment. Mutagenesis 10 (1995) 85-90.
• 14. Kuchenmeister, F., Schmezer, P., Engelhardt, G. Geneotoxic bifunctional aldehydes produce specific images in the comet assay. Mutat. Res. 419 (1998) 69-78.
• 15. Xanthoudakis, S., Miao, G., Wang, F., Pan, Y. C., Curran, T. Redox activation of Fos-Jun DNA binding activity is mediated by a DNA repair enzyme. EMBO J. 11 (1992) 3323-3335.
• 16. Fang, J. L. and Vaca, C. E. Detection of DNA adducts of acetaldehyde in peripheral white blood cells of alcohol abusers. Carcinogenesis 18 (1997) 627- 632.