McKinnon R A, McManus M E
Department of Environmental Health, University of Cincinnati, Ohio, USA.
Pathology. 1996 May;28(2):148-55. doi: 10.1080/00313029600169783.
Cytochromes P450 comprise a remarkably diverse superfamily of heme-thiolate proteins critical in the metabolism of numerous endogenous ligands and xenobiotics. Among the myriad of P450 substrates are many compounds of toxicological and pharmacological significance. The precise complement of cytochrome P450 isoforms in any given tissue may therefore be an important determinant of susceptibility to chemical-mediated toxicity. We have used a histological approach to study the distribution of individual P450s in human and rabbit gastro-intestinal tissues. We have focused primarily on P450 enzymes of importance in the metabolism of carcinogens, namely CYP1A1, CYP1A2, CYP2E1, CYP3A4/3A5 and CYP4B1. Here we give an overview of the distribution of these enzymes in human and rabbit tissues and discuss the possible toxicological implications of the results. In addition we will discuss the value of archival human tissue specimens for histological analysis of P450 distribution.
细胞色素P450构成了一个非常多样化的血红素硫醇盐蛋白超家族，对众多内源性配体和外源性物质的代谢至关重要。在众多P450底物中，有许多具有毒理学和药理学意义的化合物。因此，任何给定组织中细胞色素P450同工型的精确组成可能是化学介导毒性易感性的重要决定因素。我们采用组织学方法研究了人和兔胃肠道组织中单个P450的分布。我们主要关注在致癌物代谢中重要的P450酶，即CYP1A1、CYP1A2、CYP2E1、CYP3A4/3A5和CYP4B1。在此，我们概述了这些酶在人和兔组织中的分布，并讨论了结果可能的毒理学意义。此外，我们还将讨论存档人体组织标本用于P450分布组织学分析的价值。
