Modulation of the cytochrome P450 system as a mechanism of chemoprotection

C R Wolf, A Mahmood, C J Henderson, R McLeod, M M Manson, G E Neal, J D Hayes

Research output: Contribution to journalReview article

13 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)165-73
Number of pages9
JournalIARC Scientific Publications
Issue number139
Publication statusPublished - 1996

Fingerprint

Poisons
Cytochrome P-450 Enzyme System
Isoenzymes
Oxygenases
Cytoprotection
Cytochromes
Metabolic Networks and Pathways
Carcinogens
Enzymes

Keywords

  • Animals
  • Anticarcinogenic Agents/pharmacology
  • Carcinogens/pharmacokinetics
  • Cytochrome P-450 Enzyme Inhibitors
  • Cytochrome P-450 Enzyme System/drug effects
  • Enzyme Induction/drug effects
  • Enzyme Inhibitors/pharmacology
  • Humans
  • Inactivation, Metabolic
  • Isoenzymes/antagonists & inhibitors
  • Neoplasms/enzymology

Cite this

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title = "Modulation of the cytochrome P450 system as a mechanism of chemoprotection",
abstract = "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.",
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author = "Wolf, {C R} and A Mahmood and Henderson, {C J} and R McLeod and Manson, {M M} and Neal, {G E} and Hayes, {J D}",
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Modulation of the cytochrome P450 system as a mechanism of chemoprotection. / Wolf, C R; Mahmood, A; Henderson, C J; McLeod, R; Manson, M M; Neal, G E; Hayes, J D.

In: IARC Scientific Publications, No. 139, 1996, p. 165-73.

Research output: Contribution to journalReview article

TY - JOUR

T1 - Modulation of the cytochrome P450 system as a mechanism of chemoprotection

AU - Wolf, C R

AU - Mahmood, A

AU - Henderson, C J

AU - McLeod, R

AU - Manson, M M

AU - Neal, G E

AU - Hayes, J D

PY - 1996

Y1 - 1996

N2 - 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.

AB - 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.

KW - Animals

KW - Anticarcinogenic Agents/pharmacology

KW - Carcinogens/pharmacokinetics

KW - Cytochrome P-450 Enzyme Inhibitors

KW - Cytochrome P-450 Enzyme System/drug effects

KW - Enzyme Induction/drug effects

KW - Enzyme Inhibitors/pharmacology

KW - Humans

KW - Inactivation, Metabolic

KW - Isoenzymes/antagonists & inhibitors

KW - Neoplasms/enzymology

UR - https://www.ncbi.nlm.nih.gov/pubmed/8923029

M3 - Review article

C2 - 8923029

SP - 165

EP - 173

JO - IARC Scientific Publications

JF - IARC Scientific Publications

SN - 0300-5038

IS - 139

ER -