Baird W M, Chemerys R, Grinspan J B, Mueller S N, Levine E M
Cancer Res. 1980 Jun;40(6):1781-6.
The metabolism of [3H]benzo(a)pyrene ([3H]BP) in bovine aortic endothelial and bovine lung fibroblast-like cells in vitro was investigated. Both cell types metabolized BP to organic solvent-extractable and water-soluble metabolites. The major organic solvent-extractable metabolites were 9-hydroxy-benzo(a)pyrene and 3-hydroxybenzo(a)pyrene; 7,8-dihydro-7,8-dihydroxybenzo(a)pyrene, 9,10-dihydro-9,10-dihydroxy-benzo(a)pyrene, and BP quinones were also formed. No glucuronide or sulfate conjugates of BP metabolites were detected. When exposed to [3H]-3-hydroxybenzo(a)pyrene, both cell types metabolized this phenol to water-soluble derivatives, probably through oxidation rather than conjugation of the molecule. These results demonstrate that endothelial cells metabolze BP to a proximate carcinogenic derivative, the 7,8-dihydrodiaol. Thus, efforts to predict the biological effects of hydrocarbons of an organism must take into account possible metabolic activation by endothelial cells as well as by other target tissues. The formation of unconjugated, phenolic hydrocarbon derivatives by bovine cells suggests their use as a model system for studying the contribution of phenols to the induction of biological effects by hydrocarbons.
研究了[3H]苯并(a)芘([3H]BP)在牛主动脉内皮细胞和牛肺成纤维样细胞中的体外代谢情况。两种细胞类型都将BP代谢为有机溶剂可萃取和水溶性代谢产物。主要的有机溶剂可萃取代谢产物是9-羟基苯并(a)芘和3-羟基苯并(a)芘;还形成了7,8-二氢-7,8-二羟基苯并(a)芘、9,10-二氢-9,10-二羟基苯并(a)芘和BP醌。未检测到BP代谢产物的葡萄糖醛酸或硫酸盐结合物。当暴露于[3H]-3-羟基苯并(a)芘时,两种细胞类型都将这种酚代谢为水溶性衍生物,可能是通过分子的氧化而非结合。这些结果表明内皮细胞将BP代谢为一种近似致癌衍生物,即7,8-二氢二醇。因此,预测生物体中碳氢化合物生物效应的努力必须考虑到内皮细胞以及其他靶组织可能的代谢活化。牛细胞形成未结合的酚类碳氢化合物衍生物表明它们可作为研究酚类对碳氢化合物诱导生物效应贡献的模型系统。