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

• Published in: Journal of applied toxicology 2011-01, Vol.31 (1), p.11-19
• Main Authors: Fanelli, Silvia L., Maciel, María E., Díaz Gómez, María I., Delgado de Layño, Aurora M.A., Bietto, Florencia M., Castro, José A., Castro, Gerardo D.
• Format: Article
• Language: English
• Subjects: Acetaldehyde; Acetaldehyde - metabolism; Acetaldehyde - toxicity; alcohol; Alcohol Drinking - adverse effects; Alcoholism and acute alcohol poisoning; Alcohols; Animals; Biological and medical sciences; Breast; breast cancer; Breast Neoplasms - etiology; Ethanol; Ethanol - metabolism; Ethanol - toxicity; Ethyl alcohol; Female; Free Radicals - toxicity; Glutathione; Gynecology. Andrology. Obstetrics; Mammary gland diseases; Medical sciences; Oxidative Stress; Promotion; Rats; Rats, Sprague-Dawley; Toxicology; Tumors
• ISSN: 0260-437X; 1099-1263; 1099-1263
• DOI: 10.1002/jat.1555

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. Copyright © 2010 John Wiley & Sons, Ltd. Repetitive alcohol drinking was found to produce significant decreases in the mammary tissue content of GSH, alpha‐tocopherol and enzymes involved in tissue defense against oxidative damage. Mammary microsomal metabolism of ethanol to acetaldehyde was not induced after an acute dose of ethanol or acetone. Cytosolic pathway instead was significantly enhanced. Results suggest that while acetaldehyde accumulation in mammary tissue could be a critical event resulting from increasing production in situ, poor handling of the accumulated acetaldehyde could be also relevant.