Melikian A A, Goldin B F, Prahalad A K, Hecht S S
Naylor Dana Institute for Disease Prevention, American Health Foundation, Valhalla, New York 10595.
Chem Res Toxicol. 1990 Mar-Apr;3(2):139-43. doi: 10.1021/tx00014a009.
The effects of chronic ethanol consumption by hamsters on the binding of [3H]benzo[a]pyrene (BaP) metabolites to the DNA of cheek pouch and liver have been examined. Thirty hamsters were fed control liquid diet, and another 30 hamsters were given 6.6% v/v, 190 proof ethanol-containing diet for 28 days. Twenty-four hours after topical application of [3H]BaP to the cheek pouches, the hamsters were killed and DNA was isolated from epithelial sheets of the cheek pouches and from the liver. Two major deoxyribonucleoside adducts were detected in the hamster cheek pouch; one was identified as the N2-deoxyguanosine adduct of (+)-[3H]-7 alpha,8 beta-dihydroxy-9 beta,10 beta-epoxy-7,8,9,10-tetrahydro- BaP [(+)-anti-BPDE-dG]. The other has not yet been characterized. It was named adduct A and cochromatographed with the major adduct derived from (+)-[3H]-trans-7,8-dihydroxy-7,8- dihydrobenzo[a]pyrene [(+)-BaP-7,8-diol] in mouse skin. Chronic ethanol consumption by hamsters had no statistically significant effect on the (+)-anti-BPDE-dG adduct whereas it increased the level of adduct A by 80%. Binding of BaP metabolites to liver DNA was minor and was not influenced by ethanol. This study suggests that chronic ethanol consumption by hamsters either enhances the formation of the (+)-BaP-7,8-diol from BaP or increases oxidation of this diol and its binding to the DNA of the hamster's cheek pouch.
已研究了仓鼠长期摄入乙醇对[3H]苯并[a]芘(BaP)代谢产物与颊囊和肝脏DNA结合的影响。30只仓鼠喂食对照液体饲料,另外30只仓鼠给予含6.6% v/v、190标准酒精度乙醇的饲料,持续28天。在颊囊局部涂抹[3H]BaP 24小时后,处死仓鼠,从颊囊上皮片和肝脏中分离DNA。在仓鼠颊囊中检测到两种主要的脱氧核糖核苷加合物;一种被鉴定为(+)-[3H]-7α,8β-二羟基-9β,10β-环氧-7,8,9,10-四氢-BaP的N2-脱氧鸟苷加合物[(+)-反式-BPDE-dG]。另一种尚未鉴定。它被命名为加合物A,在小鼠皮肤中与源自(+)-[3H]-反式-7,8-二羟基-7,8-二氢苯并[a]芘[(+)-BaP-7,8-二醇]的主要加合物共色谱。仓鼠长期摄入乙醇对(+)-反式-BPDE-dG加合物没有统计学上的显著影响,而加合物A的水平增加了80%。BaP代谢产物与肝脏DNA的结合较少,且不受乙醇影响。这项研究表明,仓鼠长期摄入乙醇要么增强了BaP形成(+)-BaP-7,8-二醇的过程,要么增加了该二醇的氧化及其与仓鼠颊囊DNA的结合。