Modulation of the cytochrome P450 system as a mechanism of chemoprotection.
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.
Wolf
C R
CR
University of Dundee, Ninewells Hospital & Medical School.
Mahmood
A
A
Henderson
C J
CJ
McLeod
R
R
Manson
M M
MM
Neal
G E
GE
Hayes
J D
JD
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D002273:Carcinogens / Q000493:pharmacokinetics; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects* / Q000378:metabolism; D004790:Enzyme Induction / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D008658:Inactivation, Metabolic; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000187:drug effects* / Q000378:metabolism; D009369:Neoplasms / Q000201:enzymology / Q000517:prevention & control
D016588:Anticarcinogenic Agents; D002273:Carcinogens; D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D003577:Cytochrome P-450 Enzyme System