Ethanol inhibits benzo[a]pyrene-DNA adduct removal and increases 8-oxo-deoxyguanosine formation in human mammary epithelial cells.
Ethanol inhibits benzo[a]pyrene-DNA adduct removal and increases 8-oxo-deoxyguanosine formation in human mammary epithelial cells.
复制标题
乙醇抑制人乳腺上皮细胞中苯并[a]芘-DNA 加合物的去除并增加 8-氧代-脱氧鸟苷的形成。
DOI：
10.1016/j.canlet.2003.09.004
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发表时间：
2004
期刊：
影响因子：
9.7
通讯作者：
vanBreemen,RichardB
中科院分区：
文献类型：
--
作者：
Singletary,KeithW;Barnes,SeanL;vanBreemen,RichardB
研究了乙醇和乙醛处理对永生化人乳腺上皮细胞系MCF-10F中苯并[a]芘二醇环氧化物(BPDE)-DNA加合物去除的影响。与对照组相比，15mM和25mM乙醇处理的细胞在多个时间点上留下的BPDE-DNA加合物/单位DNA明显更多。暴露于15和25 mM乙醇的细胞中，BPDE-DNA加合物的半衰期分别为11.9和12.3 h，而对照细胞的半衰期为9.8 h。相比之下，与对照组相比，暴露于2.5 μM和5.0 μM乙醛剂量的细胞在BPDE-DNA加合物持久性方面没有明显的趋势。用乙醇处理的细胞对加合物去除的抑制与乙醇暴露导致的细胞活力的任何变化无关。然而，bp处理的细胞暴露于25mM乙醇中，与单独处理的细胞相比，8-氧-脱氧鸟苷（8-氧- deg）加合物显著增加了2倍。用BP处理和暴露于5.0 μM乙醛的细胞中，8-o - deg没有显著增加。因此，乙醇暴露于人乳腺上皮细胞与去除BPDE-DNA加合物的能力下降有关。乙醇对加合物去除的抑制作用部分可能与乙醇相关的氧化应激有关。
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.
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