Wolf C R, Mahmood A, Henderson C J, McLeod R, Manson M M, Neal G E, Hayes J D
University of Dundee, Ninewells Hospital & Medical School.
IARC Sci Publ. 1996(139):165-73.
The cytochrome P450-dependent mono-oxygenase system has evolved as one of our primary defences against toxic chemicals present in our environment. This multi-enzyme system functions as an adaptive response to environmental challenge in that exposure to specific toxic agents induces the expression of cytochrome P450 isozymes active in their metabolism. In most cases, such metabolism leads to an increased rate of chemical detoxification, but in certain cases it can also lead to an increased rate of chemical activation to toxic products. The induction of cytochrome P450s leading to cytoprotection is a major mechanism of chemoprotection, and it is well documented that this pathway prevents a large number of toxic reactions. Incredibly, despite the importance of this metabolic pathway, the effects of a wide range of chemoprotective agents with different mechanisms of action on the expression of specific cytochrome P450 isozymes remains poorly understood. In this chapter, we discess the ability of different chemical compounds to modulate cytochrome P450 both at the transcriptional and post-transcriptional levels, in a way which affects its ability to metabolize or detoxify chemical carcinogens.
细胞色素P450依赖的单加氧酶系统已演变成我们抵御环境中有毒化学物质的主要防御机制之一。这个多酶系统作为对环境挑战的一种适应性反应发挥作用，即接触特定有毒物质会诱导对其代谢具有活性的细胞色素P450同工酶的表达。在大多数情况下，这种代谢会导致化学物质解毒速率增加，但在某些情况下，它也可能导致化学物质活化成有毒产物的速率增加。导致细胞保护的细胞色素P450的诱导是化学保护的主要机制，并且有充分的文献记载该途径可防止大量毒性反应。令人难以置信的是，尽管这条代谢途径很重要，但人们对具有不同作用机制的多种化学保护剂对特定细胞色素P450同工酶表达的影响仍知之甚少。在本章中，我们探讨了不同化合物在转录和转录后水平调节细胞色素P450的能力，这种调节方式会影响其代谢或解毒化学致癌物的能力。
