Agarwal R, Coffing S L, Baird W M, Kiselyov A S, Harvey R G, Dipple A
ABL-Basic Research Program, National Cancer Institute-Frederick Cancer Research & Development Center, Maryland 21702, USA.
Cancer Res. 1997 Feb 1;57(3):415-9.
Benzo[g]chrysene (BgC) is an environmental pollutant, and recent studies have demonstrated that anti- BgC-11,12-dihydrodiol 13,14-epoxide (anti-BgCDE) is a potent mammary carcinogen in rats. To determine whether BgC can be metabolically activated to anti-BgCDE in human cells, the human mammary carcinoma cell line MCF-7 was treated with BgC and with the racemic trans-3,4- and 11,12-dihydrodiols. The DNA adducts formed in these experiments were examined using 32P-postlabeling, and specific adducts were identified through comparisons with adducts obtained by the reaction of the racemic syn- and anti-BgCDEs with calf thymus DNA and with purine deoxyribonucleoside-3'-phosphates in vitro. It was found that BgC is metabolically activated in MCF-7 cells to form major DNA adducts through both the syn- and anti-11,12-dihydrodiol 13,14-epoxide metabolites. BgC is therefore a potential environmental risk to humans. The major BgC-DNA adducts formed from both the dihydrodiol-epoxide diastereomers were deoxyadenosine adducts. Thus, BgC has DNA-binding properties that are very similar to those of the potent mammary carcinogens 7,12-dimethylbenz[a]anthracene and dibenzo[a,l]pyrene.
苯并[g]屈（BgC）是一种环境污染物，近期研究表明，反式-BgC-11,12-二氢二醇13,14-环氧化物（反式-BgCDE）是大鼠体内一种强效的乳腺癌致癌物。为了确定BgC在人类细胞中是否能代谢活化为反式-BgCDE，用人乳腺癌细胞系MCF-7分别用BgC以及外消旋的反式-3,4-和11,12-二氢二醇进行处理。使用32P后标记法检测这些实验中形成的DNA加合物，并通过与外消旋的顺式和反式-BgCDE与小牛胸腺DNA以及嘌呤脱氧核糖核苷-3'-磷酸在体外反应获得的加合物进行比较来鉴定特定加合物。结果发现，BgC在MCF-7细胞中通过顺式和反式-11,12-二氢二醇13,14-环氧化物代谢物被代谢活化，形成主要的DNA加合物。因此，BgC对人类是一种潜在的环境风险。由二氢二醇-环氧化物非对映异构体形成的主要BgC-DNA加合物是脱氧腺苷加合物。因此，BgC具有与强效乳腺癌致癌物7,12-二甲基苯并[a]蒽和二苯并[a,l]芘非常相似的DNA结合特性。
