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

• DOI: 10.1073/pnas.95.9.5275
• Publication Date: 2002-07-26T14:31:44Z
• Authors: Colin J. Henderson; Austin G. Smith; Jan Ure; Ken Brown; E. Jane Bacon; C. Roland Wolf
• Keywords: GSTP1; Glutathione S-transferase

The activity of chemical carcinogens is a complex balance between metabolic activation by cytochrome P450 monooxygenases and detoxification enzymes such as glutathione S-transferase (GST). Regulation these proteins may have profound effects on carcinogenic activity, although it has proved impossible to ascribe the observed single protein. GstP appears play very important role in carcinogenesis, precise nature its involvement unclear. We deleted murine gene cluster established skin tumorigenesis induced polycyclic aromatic hydrocarbon 7, 12-dimethylbenz anthracene tumor promoting agent 12-O-tetradecanoylphorbol-13-acetate. After 20 weeks, highly significant increase number papillomas was found GstP1/P2 null mice [GstP1/P2(-/-) mice, 179 papillomas, mean 9.94 per animal vs. GstP1/P2(+/+) 55 2.89 animal, (P < 0.001)]. This difference incidence provides direct evidence that involved drug metabolism can effect tumorigenicity, demonstrates be an determinant cancer susceptibility, particularly diseases where exposure hydrocarbons involved, for instance cigarette smoke-induced lung cancer.