Rietjens I M, Steensma A, Den Besten C, van Tintelen G, Haas J, van Ommen B, van Bladeren P J
Department of Biochemistry, Agricultural University, Wageningen, Netherlands.
Eur J Pharmacol. 1995 Dec 7;293(4):293-9. doi: 10.1016/0926-6917(95)90048-9.
The porphyrinogenic action of hexafluorobenzene was investigated and compared to that of hexachlorobenzene. Metabolite patterns in the urine of exposed rats were determined to quantify the extent of metabolism through cytochrome P450 catalysed oxidation and glutathione conjugation. Results obtained demonstrate an almost similar extent of formation of phenolic metabolites. However, in the urine of hexachlorobenzene exposed rats significantly higher levels of the N-acetyl-S-(pentahalophenyl)cysteine were observed than in the urine of hexafluorobenzene exposed rats. Hexafluorobenzene exposure did not result in induction of porphyria, whereas exposure to hexachlorobenzene did result in significantly elevated levels of urinary as well as liver porphyrins. Together these results indicate that if the reactive intermediate is indeed formed in the cytochrome P450 catalysed initial oxidative dehalogenation, the extent of its formation as well as its subsequent reactivity and reaction pathways vary with the type of the halogen substituents. Furthermore, the results seem to indicate that the extent of metabolism of hexahalogenated benzenes into urinary metabolites resulting from glutathione conjugation is a better indication of their porphyrinogenic action than their extent of metabolism to phenolic metabolites. Two explanations for this observation are presented.
研究了六氟苯的致卟啉作用，并与六氯苯进行了比较。通过测定暴露大鼠尿液中的代谢物模式，以量化细胞色素P450催化氧化和谷胱甘肽结合作用下的代谢程度。所得结果表明，酚类代谢物的生成程度几乎相似。然而，在暴露于六氯苯的大鼠尿液中，观察到的N - 乙酰 - S -（五卤代苯基）半胱氨酸水平明显高于暴露于六氟苯的大鼠尿液中的水平。暴露于六氟苯不会导致卟啉症的诱导，而暴露于六氯苯确实会导致尿液和肝脏卟啉水平显著升高。这些结果共同表明，如果反应性中间体确实在细胞色素P450催化的初始氧化脱卤反应中形成，那么其形成程度以及随后的反应活性和反应途径会因卤素取代基的类型而异。此外，结果似乎表明，六卤代苯通过谷胱甘肽结合作用代谢为尿液代谢物的程度，比其代谢为酚类代谢物的程度更能表明它们的致卟啉作用。本文提出了对这一观察结果的两种解释。
