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Increased skin tumorigenesis in mice lacking pi class glutathione S-transferases.

TitleIncreased skin tumorigenesis in mice lacking pi class glutathione S-transferases.
Publication TypeJournal Article
Year of Publication1998
AuthorsHenderson CJ, Smith AG, Ure J, Brown K, Bacon EJ, Wolf CR
JournalProc Natl Acad Sci U S A
Volume95
Issue9
Pagination5275-80
Date Published1998 Apr 28
ISSN0027-8424
Keywords9,10-Dimethyl-1,2-benzanthracene, Animals, Cloning, Molecular, Cytosol, Female, Genes, Glutathione, Glutathione S-Transferase pi, Glutathione Transferase, Isoenzymes, Mice, Mice, Knockout, Multigene Family, Neoplasms, Experimental, RNA, Messenger, Sequence Deletion, Skin Neoplasms, Tissue Distribution
Abstract

The activity of chemical carcinogens is a complex balance between metabolic activation by cytochrome P450 monooxygenases and detoxification by enzymes such as glutathione S-transferase (GST). Regulation of these proteins may have profound effects on carcinogenic activity, although it has proved impossible to ascribe the observed effects to the activity of a single protein. GstP appears to play a very important role in carcinogenesis, although the precise nature of its involvement is unclear. We have deleted the murine GstP gene cluster and established the effects on skin tumorigenesis induced by the polycyclic aromatic hydrocarbon 7, 12-dimethylbenz anthracene and the tumor promoting agent 12-O-tetradecanoylphorbol-13-acetate. After 20 weeks, a highly significant increase in the number of papillomas was found in the GstP1/P2 null mice [GstP1/P2(-/-) mice, 179 papillomas, mean 9.94 per animal vs. GstP1/P2(+/+) mice, 55 papillomas, mean 2.89 per animal, (P

Alternate JournalProc. Natl. Acad. Sci. U.S.A.
PubMed ID9560266
PubMed Central IDPMC20251