Ethanol metabolism to acetaldehyde and free radicals in breast subcellular fractions and mammary epithelial cell injury

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

Tampere, Finland

Congreso; 10th International Congress of Toxicology.ICTX 2004; 2004

Finnish Society of Toxicology. International Union of Toxicology (IUTOX).

There is evidence supporting an association  between alcohol intake and risk of breast cancer. Our laboratory is testing the working hypothesis that biotransformation ofl alcoho(ETOH) to acetaldehyde (AC) and 1.hydroxyethyl free radicals (1HEt) in situ might playa role in the process. We recently reported ETOH activation to AC and 1HEt  in cytosolic fraction mediated b xanthine oxidoreductase (XOR). Now, we report that rat breast microsomes also bioactivate ETOH. Sprague-Dawley female rats (250-300g) were used. There are in breast microsomes NADPH and air dependent pathways of ETOH bioactivation to AC. The NADPH-dependent pathway is not inhibited by CO:O2 (80:20) or by SKF 525A 1mM; or desferrioxamine, is strongly inhibited by diphenyleneiodonium (DPI) 10 uM and partially inhibited by methylmercaptoimidazol (MMI) and thiobenzamide. This suggest that cytochrome P450 or iron are not involved in the process and that part of it but not all, might be FMO mediated. Other part might be P450 reductase mediated. The NADPH independent process is partially inhibited by MMI, TBA and strongly inhibited by DPI and its nature remains unclear. NADPH and air dependent ETOH biotransformation also leads to generation of detectable hydroxyl and 1HEt radicals. The bioactivation of ETOH to AC and free radicals in breast microsomes and cytosol might be involved in mammary cancer promotion observed in alcohol consumers.