Effect of repetitive alcohol drinking on rat breast ultrstructure and EtOH metabolism to acetaldehyde and mammary tissue tendency to genetaye reactive oxygen species

M.E. MACIEL, C. RODRIGUEZ DE CASTRO, S.L. FANELLI, M.I. DÍAZ GÓMEZ, E. CIGNOLI DE FERREYRA, G.D. CASTRO AND J.A. CASTRO.

Fort Lauderdale, Florida

Congreso; 26th Annual Meeting of the Research Society on Alcoholism and the 12th Congress of the International Society for Biomedical Research on Alcoholism; 2003

International Society for Biomedical Research on Alcoholism

Recent studies from our laboratory evidenced that the breast cytosolic xanthine oxidoreductase (XOR) activates EtOH to AC and free radicals and that there is a microsomal non-P450 dependent activation of EtOH to AC but not to free radicals, requering NADPH and oxygen. (Toxicology 160: 11-18 (2001) and Terat. Carcinog. Mutag. 22: 1-10 (2002). Now we report that repetitive EtOH administration during 28 days through the standard Lieber & De Carli diet led to 80% increase of XOR pathway and to 27% induction of the microsomal one. The t-butylhydroperoxide promoted chemiluminiscence of breast homogenates in the EtOH treated animals was significantly enhanced in relation to controls, evidencing the tendency of the EtOH group to generate ROS. The XOR activity as evidenced by histochemistry was located in the epithelial cells. Accordinly, electron microscopy observation of those cells in the EtOH treated animals revealed the presence of significant ultrastructural deleterious effects, including their altered architecture. Their nuclei show irregular forms having invaginations of the nuclear envelopie and margination of the chromatin . Sometimes the chanel contain filamentous material oriented to cytoplasm. The basal lamina are frequently hazy and more thick. In summary, breast epithelial cells are able to bioactivate EtOH to reactive moieties, which may harm their ultrastructure and function.