Shou M G, Yang S K
Department of Pharmacology, F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20889-4799.
Carcinogenesis. 1990 Nov;11(11):2037-45. doi: 10.1093/carcin/11.11.2037.
Products formed in the metabolism of 2S-hydroxy-3-methylcholanthrene (2S-OH-3MC) by liver microsomes prepared from phenobarbital-treated rats were isolated by sequential use of reversed-phase and normal-phase HPLC. Metabolites of 2S-OH-3MC were characterized by UV-visible absorption, mass and circular dichroic spectra, and chiral stationary phase HPLC analyses. The metabolites that had been identified were 2S-hydroxy-3-hydroxymethylcholanthrene (2S-OH-3-OHMC), 3MC-2-one, 3MC-2-one 9,10-dihydrodiol, 8-hydroxy-2S-OH-3MC, a pair of stereoisomers 3MC (trans)-1R,2R-diol and (cis)-1S,2R-diol in a ratio of approximately 11:89, a pair of diastereomers 2S-OH-3MC 9R,10R-dihydrodiol and 2S-OH-3MC 9S,10S-dihydrodiol in a ratio of approximately 9:1, and a pair of diastereomers 2S-OH-3MC 11R,12R-dihydrodiol and 2S-OH-3MC 11S,12S-dihydrodiol in a ratio of approximately 77:23. A few tentatively identified minor metabolites were 3-OHMC trans-1R,2R-diol, 10-hydroxy-2S-OH-3MC, a 9,10-dihydrodiol derived from 3MC cis-1S,2R-diol, and a 11,12-dihydrodiol and two diastereomeric 9,10-dihydrodiols derived from 2S-OH-3-OHMC. Since the racemic 2-OH-3MC is a known potent carcinogen and 2S-OH-3MC is the most abundant metabolite of 3MC, some of the 2S-OH-3MC metabolites identified in this study may be further converted to proximate and ultimate carcinogens which may contribute to the overall carcinogenicity exhibited by 3MC.
采用反相和正相高效液相色谱法，从经苯巴比妥处理的大鼠肝脏微粒体中分离出2S - 羟基 - 3 - 甲基胆蒽（2S - OH - 3MC）代谢过程中形成的产物。通过紫外 - 可见吸收光谱、质谱、圆二色光谱以及手性固定相高效液相色谱分析对2S - OH - 3MC的代谢产物进行了表征。已鉴定出的代谢产物有2S - 羟基 - 3 - 羟甲基胆蒽（2S - OH - 3 - OHMC）、3MC - 2 - 酮、3MC - 2 - 酮9,10 - 二氢二醇、8 - 羟基 - 2S - OH - 3MC、一对比例约为11:89的立体异构体3MC（反式）- 1R,2R - 二醇和（顺式）- 1S,2R - 二醇、一对比例约为9:1的非对映异构体2S - OH - 3MC 9R,10R - 二氢二醇和2S - OH - 3MC 9S,10S - 二氢二醇、以及一对比例约为77:23的非对映异构体2S - OH - 3MC 11R,12R - 二氢二醇和2S - OH - 3MC 11S,12S - 二氢二醇。初步鉴定出的一些次要代谢产物为3 - OHMC反式 - 1R,2R - 二醇、10 - 羟基 - 2S - OH - 3MC、一种源自3MC顺式 - 1S,2R - 二醇的9,10 - 二氢二醇、以及一种源自2S - OH - 3 - OHMC的11,12 - 二氢二醇和两种非对映异构体9,10 - 二氢二醇。由于外消旋2 - OH - 3MC是一种已知的强致癌物，且2S - OH - 3MC是3MC最丰富的代谢产物，本研究中鉴定出的一些2S - OH - 3MC代谢产物可能会进一步转化为近端和最终致癌物，这可能会导致3MC表现出的整体致癌性。
