Alcohol drinking, acetaldehyde accumulation and oxidative stress promotion in mammary tissue. Their potential role in ethanol induced breast cancer

CASTRO G.D; DELGADO A.M.A; FANELLI S.L; MACIEL M.E; DÍAZ GÓMEZ M.I; CASTRO J.A

Washington, D.C.

Conferencia; International Research Conference on Food, Nutrition and Cancer; 2006

World Cancer Research Fund International. American Institute for Cancer Research.

In previous studies from our laboratory the presence of several pathways of metabolic activation of ethanol to acetaldehyde and hydroxyl free radicals as well as the promotion of oxidative tress was reported. In the present studies we tested the possibility that after alcohol drinking, acetaldehyde accumulated in mammary tissue to reach concentrations higher than in blood. Three different doses of alcohol were tested and acetaldehyde concentrations in breast, liver and blood were measured at times ranging from 1 to 24 hours.  We also determined alcohol dehydrogenase; aldehyde dehydrogenase and CYP2E1 mediated p-nitrophenol hydroxylase activities. Oxidative stress induced hydroperoxyde formation studies, as determined the xylenol orange procedure; alpha tocopherol and GSH content are in course for each dose at different times of exposure. At present hydroperoxyde levels led to increased values and GSH to decreased content at 24 hours for the higher doses tested. The obtained results showed that acetaldehyde concentrations at the three alcohol doses tested (low, medium and high) were always higher than in blood. Peak concentrations of acetaldehyde in liver, while higher than those in breast, appeared to decrease to blood levels following a similar time sequence. Limited activities of alcohol dehydrogenase and aldehyde dehydrogenase in mammary tissue were observed. The microsomal CYP2E1-mediated p-nitrophenol hydroxylase in mammary tissue was several times smaller than in liver. In summary, results suggest that the mutagen acetaldehyde, either formed in situ or, even in small amounts, continuously arriving via blood, tends to accumulate in mammary tissue as a consequence of a limited capacity of it for detoxification. During the period of alcohol exposure, lipid hydroperoxyde formation increased and the GSH and alpha tocopherol levels in mammary tissue were decreased only at the highest dose tested.Supported by grants from ANPCyT-SECyT (PICT 05-6045) and from UNSAM (PIB S05-03)