Oravec C T, Daniel F B, Wong L K
Cancer Lett. 1983 Nov;21(1):43-55. doi: 10.1016/0304-3835(83)90081-2.
The metabolism of 7,12-dimethylbenz[a]anthracene (DMBA) and its non-carcinogenic 2-fluoro analogue (2F-DMBA) by Syrian hamster embyro (SHE) cells has been studied using high pressure liquid chromatography (HPLC) and fluorescence spectroscopy. Metabolites produced by SHE cells were compared chromatographically to those produced on a larger scale by liver microsomal preparations and previously identified by gas chromatography and mass spectrometry. At least 2 (possibly 3) phenol metabolites, none of which appear to be in the A-ring, were formed from [3H] 2F-DMBA and totalled only 3% of the organic extractable activity present in the media at 24 h. On the other hand, 3 A-ring phenols (DMBA-2-ol, DMBA-3-ol and DMBA-4-ol) comprising almost 12% of the total organic extractable radioactivity at 24 h were identified as metabolites in SHE cell culture media. For both hydrocarbons the major organic extractable metabolite present at 24 h was the respective 8,9-dihydro-dihydroxydiol (DMBA 45%, 2F-DMBA 39%). Thus, substitution of fluorine for hydrogen at the 2-carbon of DMBA appears to block or greatly reduce the A-ring metabolism of this compound but has relatively little effect on D-ring oxidation. Therefore loss of the carcinogenic/mutagenic activity of DMBA correlates with the extent of A-ring metabolism including, possibly, the bay region diol epoxide.
利用高压液相色谱法（HPLC）和荧光光谱法，对叙利亚仓鼠胚胎（SHE）细胞代谢7,12 - 二甲基苯并[a]蒽（DMBA）及其非致癌性2 - 氟类似物（2F - DMBA）的情况进行了研究。将SHE细胞产生的代谢产物通过色谱法与肝微粒体制剂大规模产生的代谢产物进行比较，后者先前已通过气相色谱法和质谱法鉴定。由[³H] 2F - DMBA形成了至少2种（可能3种）酚类代谢产物，其中没有一种似乎在A环中，在24小时时这些代谢产物仅占培养基中可有机萃取活性的3%。另一方面，在SHE细胞培养基中鉴定出3种A环酚（DMBA - 2 - 醇、DMBA - 3 - 醇和DMBA - 4 - 醇），在24小时时它们占总有机可萃取放射性的近12%。对于这两种碳氢化合物，在24小时时存在的主要有机可萃取代谢产物是各自的8,9 - 二氢 - 二羟基二醇（DMBA为45%，2F - DMBA为39%）。因此，在DMBA的2 - 碳位用氟取代氢似乎会阻断或极大地减少该化合物的A环代谢，但对D环氧化的影响相对较小。所以，DMBA致癌/致突变活性的丧失与A环代谢的程度相关，这可能包括湾区二醇环氧化物。
