Further studies on the potential contribution of acetaldehyde accumulation and oxidative stress in rat mammary tissue in the alcohol drinking promotion of breast cancer.

There is available evidence supporting a positive association between alcohol intake and risk of breast cancer. However, there is limited information regarding possible mechanisms for this effect. Past studies from our laboratory suggest that acetaldehyde accumulation in mammary tissue after alcohol intake may be of particular relevance and that cytosolic and microsomal in situ bioactivation of ethanol to acetaldehyde and free radicals and the resulting stimulation of oxidative stress could be a significant early event related to tumor promotion. In the present studies repetitive alcohol drinking for 28 days was found to produce significant decreases in the mammary tissue content of GSH and alpha tocopherol and in glutathione S-transferase or glutathione reductase activities. In contrast, glutathione peroxidase activity was slightly increased. Malondialdehyde determinations did not show the occurrence of lipid peroxidation while the xylenol orange procedure gave positive results. The mammary microsomal metabolism of ethanol to acetaldehyde was not induced after an acute dose of ethanol or acetone able to induce the activity of its liver counterpart. The cytosolic pathway of alcohol metabolism instead was significantly enhanced by these two treatments. No increased generation of comet images was found either in mammary tissue or in liver under the experimental conditions tested. Results suggest that, while acetaldehyde accumulation in mammary tissue could be a critical event resulting from increasing production of acetaldehyde in situ plus an additional amount of it arriving via blood, other factors such as poor handling of the accumulated acetaldehyde could be also relevant.

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.