Ethanol-induced oxidative stress and acetaldehyde formation in rat mammary tissue: a potential factor involved in alcohol drinking promotion of breast cancer

GERARDO D. CASTRO; CARMEN RODRÍGUEZ DE CASTRO; MARÍA EUGENIA MACIEL; SILVIA L.FANELLI; ELIDA CIGNOLI DE FERREYRA; MARÍA I. DÍAZ GÓMEZ; JOSÉ A. CASTRO

TOXICOLOGY

Elsevier Science. Ireland Ltd

Lugar: Irlanda; Año: 2006 vol. 219 p. 208 - 219

0300-483X

Recent studies from our laboratory provided evidence that part of the carcinogenic effects of ethanol consumption might be related to its in situ metabolism at cytosolic and microsomal levels, to the mutagen acetaldehyde and to hydroxyl and 1-hydroxyethyl radicals.In this work, we report on our experiments where Sprague Dawley female rats were exposed to the standard Lieber & De Carli diet for 28 days. We observed: the induction of the (xanthineoxidoreductase mediated) cytosolic and microsomal (lipoxygenase mediated) pathways of ethanol metabolism; promotion of oxidative stress as shown by increased formation of lipid hydroperoxides; delay in the tbutylhydroperoxide induced chemiluminiscence, and a significant decrease in protein sulfhydryls. In addition, the epithelial cells showed ultrastructural alterations consisting of markedly irregular nuclei, with frequent invaginations at the level ofthe nuclear envelope, condensation of chromatin around the inner nuclear membrane, and marked dilatation of the nuclear pores showing filamentous material exiting to the cytoplasm. In conclusion, the presence in mammary epithelial cells of cytosolic and microsomal pathways of ethanol bioactivation to carcinogenic and to tumorigenic metabolites might play a role in alcohol promotionof breast cancer.