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

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 t-butylhydroperoxide 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 of the 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 promotion of breast cancer.Fil: Castro, Gerardo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Gp.citefa - Centro de Investigaciones Toxicológicas (i); ArgentinaFil: Rodríguez de Castro, Carmen. Consejo Nacional de Investigaciones Científicas y Técnicas. Gp.citefa - Centro de Investigaciones Toxicológicas (i); ArgentinaFil: Maciel, Maria Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Gp.citefa - Centro de Investigaciones Toxicológicas (i); ArgentinaFil: Fanelli, Silvia Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Gp.citefa - Centro de Investigaciones Toxicológicas (i); Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Limnología "Dr. Raúl A. Ringuelet". Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Instituto de Limnología; ArgentinaFil: Ferreyra, Elida Vilma. Consejo Nacional de Investigaciones Científicas y Técnicas. Gp.citefa - Centro de Investigaciones Toxicológicas (i); ArgentinaFil: Diaz Gomez, Maria Isabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Gp.citefa - Centro de Investigaciones Toxicológicas (i); ArgentinaFil: Castro, Jose Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Gp.citefa - Centro de Investigaciones Toxicológicas (i); Argentin