Ethanol inhibits benzo[a]pyrene-DNA adduct removal and increases 8-oxo-deoxyguanosine formation in human mammary epithelial cells

• Published in: Cancer letters Vol. 203; no. 2; pp. 139 - 144
• Main Authors: Singletary, Keith W., Barnes, Sean L., van Breemen, Richard B.
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 2004; Elsevier Limited
• Subjects: 8-oxo-deoxyguanosine; Acetaldehyde - pharmacology; Benzo(a)pyrene - pharmacology; Breast cancer; Breast Neoplasms - prevention & control; Carcinogenesis; Carcinogens; Cell culture; Cell Line, Tumor; Dehydrogenases; Deoxyguanosine - analogs & derivatives; Deoxyguanosine - biosynthesis; Deoxyribonucleic acid; DNA; DNA Adducts; DNA Damage; DNA repair; Enzymes; Epithelial Cells - drug effects; Ethanol; Ethanol - pharmacology; Experiments; Free radicals; Humans; Mammary Glands, Human - cytology; Mammary Glands, Human - drug effects; Metabolites; Oxidative Stress; Oxygen - metabolism; Proteins; Time Factors; 8-oxo-deoxyguanosine; DNA adducts; Ethanol; Carcinogenesis
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/j.canlet.2003.09.004

The effect of ethanol and acetaldehyde treatment on the removal of benzo[a]pyrene diol-epoxide (BPDE)-DNA adducts in the immortalized, human mammary epithelial cell line MCF-10F was examined. Treatment of cells with 15mM and 25mM ethanol resulted in significantly more BPDE-DNA adducts/unit DNA remaining at multiple time points, compared to controls. The half-life of BPDE-DNA adducts in cells exposed to both 15 and 25 mM ethanol were 11.9 and 12.3 h, respectively, compared to a half-life of 9.8 h for the control cells. In contrast, for cells exposed to acetaldehyde at doses of 2.5 and 5.0 μM no significant trend in BPDE-DNA adduct persistence occurred, compared to controls. The inhibition of adduct removal for cells treated with ethanol was not associated with any changes in cell viability due to ethanol exposure. However, BP-treated cells exposed to 25mM ethanol exhibited a significant 2-fold increase in 8-oxo-deoxyguanosine (8-oxo-deG) adducts compared to BP-treated cells alone. No significant increase in 8-oxo-deG was observed for cells treated with BP and exposed to 5.0 μM acetaldehyde. Thus, ethanol exposure of human mammary epithelial cells is associated with a decreased capacity to remove BPDE-DNA adducts. This inhibitory effect of ethanol on adduct removal in part may be related to ethanol-associated oxidative stress.