Relevance of the deletion polymorphisms of the glutathione S-transferases GSTT1 and GSTM1 in pharmacology and toxicology

Bolt, H. M. and Thier, R. (2006) Relevance of the deletion polymorphisms of the glutathione S-transferases GSTT1 and GSTM1 in pharmacology and toxicology. Current Drug Metabolism, 7 6: 613-628. doi:10.2174/138920006778017786


Author Bolt, H. M.
Thier, R.
Title Relevance of the deletion polymorphisms of the glutathione S-transferases GSTT1 and GSTM1 in pharmacology and toxicology
Journal name Current Drug Metabolism   Check publisher's open access policy
ISSN 1389-2002
Publication date 2006-08
Sub-type Critical review of research, literature review, critical commentary
DOI 10.2174/138920006778017786
Volume 7
Issue 6
Start page 613
End page 628
Total pages 16
Editor Chandra Prakash
Place of publication Hilversum, Netherlands
Publisher Bentham Science Publ Ltd
Collection year 2006
Language eng
Subject C1
320504 Toxicology (incl. Clinical Toxicology)
321201 Environmental and Occupational Health and Safety
321213 Human Bioethics
730299 Public health not elsewhere classified
Abstract Although cytosolic glutathione S-transterase (GST) enzymes occupy a key position in biological detoxification processes, two of the most relevant human isoenzymes. GST1-1 and GSTM1-1, are genetically deleted (non-functional alleles GSTT1*0 and GsTM1*0) in a high percentage of the human population, with major ethnic differences. The structures of the GSTT and GSTM gene areas explain the underlying genetic processes. GSTT1-1 is highly conserved during evolution and plays a major role in phase-II biotransformation of a number of drugs and industrial chemicals. e.g. cytostatic drugs, hydrocarbons and halogenated hydrocarbons. GSTM1-1 is particularly relevant in the deactivation of carcinogenic intermediates of polycyclic aromatic hydrocarbons. Several lines of evidence Suggest that hGSTT1-1 and/or hGSTM1-1 play a role in the deactivation of reactive oxygen species that are likely to be involved in cellular processes of inflammation, ageing and degenerative diseases. There is cumulating evidence that combinations of the GSTM1*0 state with other genetic traits affecting the metabolism of carcinogens (CYP1A1, GSTP1) may predispose the aero-digestivc tract and lung, especially in smokers, to a higher risk of cancer. The GSTM1*0 status appears also associated with a modest increase in the risk of bladder cancer, consistent with a GSTM1 interaction with carcinogenic tobacco smoke constituents. Both human GST deletions, although largely counterbalanced by overlapping substrate affinities within the GST superfamily, have consequences when the organism comes into contact with distinct man-made chemicals. This appears relevant in industrial toxicology and in drug metabolism.
Keyword Glutathione S-transferases
Gstm1
Gstt1
Enzyme Polymorphisms
Deletion Polymorphisms
Chronic Diseases
Cancer
Biochemistry & Molecular Biology
Pharmacology & Pharmacy
Breast-cancer Risk
Systemic-lupus-erythematosus
Polymerase-chain-reaction
Tobacco-related Cancers
Trans-stilbene Oxide
Cell Lung-cancer
Ethylene-oxide
Genetic Polymorphisms
Methyl-chloride
Neck-cancer
Q-Index Code C1
Additional Notes This document is a journal review.

Document type: Journal Article
Sub-type: Critical review of research, literature review, critical commentary
Collections: Excellence in Research Australia (ERA) - Collection
2007 Higher Education Research Data Collection
School of Biomedical Sciences Publications
 
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Created: Wed, 15 Aug 2007, 09:10:49 EST