Ethanol induced oxidative stress and acetaldehyde formation in situ. A potential mechanism for alcohol drinking promotion of breast cancer

RODRIGUEZ DE CASTRO C; MACIEL M.E; FANELLI S.L; CIGNOLI DE FERREYRA E.V; DÍAZ GÓMEZ M.I; CASTRO J.A.

San Diego, California

Congreso; Experimental Biology 2005; 2005

American Society for Biochemistry and Molecular Biology

Moderate levels of drinking alcohol (EtOH) increase the risk of breast cancer. The mechanism remains unknown. Recent studies showed that carcinogenic effects of EtOH consumption might be related to its in situ activation to the mutagen acetaldehyde (AC) and to free radicals. Here we report an additional source of AC in breast, at mitochondrial level via a rotenone-insensitive NADH-dependent pathway, which is mediated by a diphenyleneiodonium-inhibible flavoenzyme from its outer membrane. When SD female rats were exposed to the standard Lieber & De Carli diet for 28 days, evidence of significative oxidative stress in mammary tissue was observed, as determined by protein carbonyls; protein sulfhydryls; delay in t-butylhydroperoxide-induced chemiluminiscence; and induction of cytosolic xanthine oxidoreductase (XOR). The XOR activity was detected by histochemistry in the epithelial cells. These cells evidenced also ultrastructural alterations: markedly irregular nuclei, with frequent invaginations, condensation of chromatin around the inner nuclear membrane, and dilatation of the nuclear pores showing filamentous material exiting to cytoplasm. In conclusion, the presence in breast epithelial cells of the here reported pathways of EtOH bioactivation to carcinogenic AC and tumor promoting radicals may play a role in alcohol promotion of breast cancer. Supported by FONCyT and UNSAM, Argentina