1和3—硝基苯并[a]芘混合物在大鼠肝微粒体中代谢产物的探讨

本文研究用3-甲基胆蒽诱导大鼠肝微粒体与等量1-和3-硝基苯并[a]芘混合物在体外有氧条件下进行培培养,分析代谢产物和代谢速率,并同单纯的1-硝基苯并[a]芘和3-硝基苯[a]芘的代谢产物进行比较。结果表明,1-和3-硝基苯并[a]芘混合物的代谢产物与单纯的1-硝基苯并[a]和3-硝基苯并[a]芘的代谢产物是相同的,两者按摩尔比等量混合后的代谢速度也是一致的;需要把高压液相色谱仪的反相柱和正相柱结合起来使用,才能把1-和3-硝基苯并[a]芘混合物的代谢产物完全分开。

Metabolism of the 1-and 3-Nitrobenzo[a] pyrene Mixture by Rat Liver Microsomes

1-and 3-nitrobenzo[a]pyrenes ( nitro-BaP ) are mutagenic and carcinogenic environmental contaninants. Although metabolism of 1-and 3-nitro-BaP has been studied individually, metabolism of the mixture has never been reported. In this paper, we describe metabolism of the 1-and 3-nitro-BaP mixture (in an equal ratio ) by liver microsomes of rats pretreated with 3-methylcholanthrene. The incubation products 1-nitro-BaP trans-7, 8-dihydrodiol, 1-nitro-BaP trans-9, 10-dihydrodiol, 3-nitro-BaP trans-7, 8-dihydrodiol, 3-nitro-BaP trans-9, 10-dihydrodiol were first separated and identified. Upon determining the HPLC peak area and comparing the UV-visible molar extinction coefficient at 254nm, the metabolism rate between 1-and 3-nitro-BaP was found to be similar. These results indicate that, (i)metabolism of the 1-and 3-nitro-BaP mixture yields similar metabolism pattern as those obtained from the metabolism of 1-nitro-BaP or 3-nitro-BaP; ( ii ) the metabolism rate between 1-and 3-nitro-BaP is similar; and ( iii ) it requires both the reversed-phase and normal-phase HPLC for complete separation of the isomeric 1-and 3-nitro-BaP trans-dihydrodiol metabolites, since all these trans-dihydrodiols have been previously found to be activated metabolites of both 1-and 3-nitro-BaP and since these metabolites are formed from metabolism of the 1-and 3-nitro-BaP mixture, our results suggest that both 1-and 3-nitro-BaP can be hazardous to human health.