The in vitro genotoxicity of ethanol and acetaldehyde

Abstract

Ability of ethanol to produce chromosomal changes has been controversial in past many years; nevertheless many recent studies have shown that ethanol itself produces genotoxic effects like acetaldehyde. This study was carried out to evaluate the ability of ethanol and its metabolite acetaldehyde to induce chromosomal changes using in vitro CBMN assay (Cytokinesis Blocked Micronucleus assay) in conjunction with immunofluorescent labeling of kinetochores. Kinetochore staining was used with a view to differentiate, between the genotoxic effects of both chemicals, and ascertain the mechanisms of genotoxicity induction by ethanol and acetaldehyde. Both ethanol and acetaldehyde produced statistically significant (P<0.05) dose dependent increase in MN induction as compared with the controls over the dose range tested. Kinetochore analysis proved that the MN induced in ethanol were originated by an aneugenic mechanism, whereas in the case of acetaldehyde most of the MN had originated by a clastogenic mechanism. This not only confirms the ability of ethanol to produce DNA damage in vitro but it also establishes the efficacy of CBMN assay to detect and differentiate between the genotoxic effects of different genotoxins. Here we report that ethanol is itself genotoxic, at least in vitro, and produces genotoxic effects mainly through an aneugenic mechanism whereas its metabolite acetaldehyde is a clastogen.