PERSONAL DE APOYO
FANELLI Silvia Laura
congresos y reuniones científicas
Título:
Ethanol induced oxidative stress and acetaldehyde formation in rat mammary tissue. A potential mechanism for alcohol drinking promotion of breast cancer
Autor/es:
CASTRO G.D., RODRIGUEZ DE CASTRO C., MACIEL M.E., FANELLI S.L, CIGNOLI DE FERREYRA E.V., DÍAZ GÓMEZ M.I: AND CASTRO J.A.
Lugar:
Mendoza, Argentina
Reunión:
Congreso; VI Congreso Latinoamericano de Mutagénesis Carcinogénesis Ambiental. XIV Congreso Argentino de Toxicología.; 2005
Institución organizadora:
asociación Toxicológica Argentina
Resumen:
Recent studies from our laboratory provided evidence that 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 radicals. In this work we report that when Sprague-Dawley female rats were exposed to the standard Lieber & De Carli diet for 28 days we observed: 1) Induction of the cytosolic and microsomal pathways of ethanol metabolism; 2) Promotion of oxidative stress as evidenced by increased formation of lipid hydroperoxides; delay in the t-butylhydroperoxide induced chemiluminiscence, significant increases in protein oxidation (increased protein carbonyls and decreased protein sulfhydryls); and induction of xanthine oxidoreductase activity. An additional pathway for ethanol metabolism to acetaldehyde was observed in mitochondria, via a rotenone insensitive NADH-dependent bioactivation. The epithelial cells evidenced marked 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 cytoplasm. In conclusion, the presence in mammary epithelial cells of cytosolic, microsomal and the here reported mitochondrial pathways of ethanol bioactivation to carcinogenic and tumor promoting metabolites might play a role in alcohol promotion of breast cancer. Supported by a grant of the University of San Martín (PIDA UF015).