Ethanol inhibits benzo[a]pyrene-DNA adduct removal and increases 8-oxo-deoxyguanosine formation in human mammary epithelial cells.
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 15 mM and 25 mM 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 microM 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 25 mM 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 microM 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.
Singletary
Keith W
KW
Department of Food Science and Human Nutrition, University of Illinois, 467, Bevier Hall, 905 South Goodwin Avenue, Urbana-Champaign, Urbana, IL, USA. kws@uiuc.edu
Barnes
Sean L
SL
van Breemen
Richard B
RB
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000079:Acetaldehyde / Q000494:pharmacology; D001564:Benzo(a)pyrene / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000517:prevention & control; D045744:Cell Line, Tumor; D018736:DNA Adducts; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000096:biosynthesis*; D004847:Epithelial Cells / Q000187:drug effects*; D000431:Ethanol / Q000494:pharmacology*; D006801:Humans; D042361:Mammary Glands, Human / Q000166:cytology* / Q000187:drug effects; D018384:Oxidative Stress; D010100:Oxygen / Q000378:metabolism; D013997:Time Factors
D018736:DNA Adducts; D001564:Benzo(a)pyrene; D000431:Ethanol; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine; D000079:Acetaldehyde; D010100:Oxygen