Ethanol-induced oxidative stress and acetaldehyde formation in rat mammary tissue: Potential factors involved in alcohol drinking promotion of breast cancer

Centro de Investigaciones Toxicológicas (CEITOX), CITEFA/CONICET, J.B. de La Salle 4397, B1603ALO Villa Martelli, Provincia de Buenos Aires, Argentina.
Toxicology (Impact Factor: 3.62). 03/2006; 219(1-3):208-19. DOI: 10.1016/j.tox.2005.11.019
Source: PubMed


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.

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    • "In effect, significantly higher levels of chemiluminescence were emitted by uterine horn homogenates challenged with t-butylhydroperoxide from alcohol treated rats than those from untreated control animals (Figure 4). This finding suggests that defenses against the oxidative challenge in alcohol treated animals could be significantly decreased [12, 41]. "
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    ABSTRACT: After alcohol exposure through a standard Lieber and De Carli diet for 28 days, a severe atrophy in the rat uteirne horn was observed, accompanied by significant alterations in its epithelial cells. Microsomal pathway of acetaldehyde production was slightly increased. Hydroxyl radicals were detected in the cytosolic fraction, and this was attributed to participation of xanthine oxidoreductase. They were also observed in the microsomal fraction in the presence of NADPH generating system. No generation of 1-hydroxyethyl was evidenced. The t -butylhydroperoxide-induced chemiluminescence analysis of uterine horn homogenates revealed a significant increase in the chemiluminiscence emission due to ethanol exposure. In the animals repeatedly exposed to alcohol, sulfhydryl content from uterine horn proteins was decreased, but no significant changes were observed in the protein carbonyl content from the same samples. Minor but significant decreasing changes were observed in the GSH content accompanied by a tendency to decrease in the GSH/GSSG ratio. A highly significant finding was the diminished activity content of glutathione peroxidase. Results suggest that acetaldehyde accumulation plus the oxidative stress may play an additional effect to the alcohol-promoted hormonal changes in the uterus reported by others after chronic exposure to alcohol.
    Journal of Toxicology 11/2013; 2013(3):161496. DOI:10.1155/2013/161496
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    ABSTRACT: 1. For decades, it has been well documented that alcohol intake increases risk for cancers of the upper aerodigestive tract (oral cavity, pharynx, larynx, and esophagus), especially at high levels of intake, as well as for breast, colon, and liver cancers. 2. Many types of cancer associations were observed for all types of alcoholic beverages, suggesting that ethanol is the main carcinogenic constituent of alcohol drinks. 3. Alcohol has multiple actions in modifying carcinogenesis, not only directly, such as disordering cell membranes, but also indirectly, such as a consequence of ethanol oxidation to acetaldehyde and other reactive intermediates. 4. The magnitude, specificity, and variability of ethanol’s actions can depend on the dose and duration of exposure and on specific biochemical and molecular characteristics of the tissues to which ethanol comes in contact. 5. The possible mechanisms underlying alcohol’s carcinogenicity include the causation of DNA damage by alcohol’s metabolic product acetaldehyde, alcohol’s effect in increasing estrogen levels, alcohol being a solvent for carcinogens, alcohol-induced generation of reactive oxygen species, alcohol-associated alterations in nutritional status, and deleterious effects of alcohol on the host immune system.
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