Overexpression of human glutathione S-transferase pi protects NIH 3T3 cells against (+/-)anti BPDE cytotoxicity but not tumor formation.
In order to explore the protective function of human glutathione S-transferase pi (GST-pi) in vitro and in vivo, transfected NIH 3T3 clones were examined in cytotoxicity assays using the carcinogen (+/-)anti-benzo(a)pyrene 7,8-diol-9,10-epoxide (BPDE) or inoculated into nude mice and treated with the carcinogen benzo(a)pyrene (BP) to induce tumor formation. The human GST-pi cDNA under the control of the murine alpha 2(I)collagen promoter was transfected into NIH 3T3 cells and G418 resistant clones were analyzed by Southern, northern, western, and two-dimensional analysis. Clone A2 stably expressed human GST-pi and has 2.5-fold greater activity toward the substrate 1-chloro-2,4-dinitrobenzene and a 1.7-fold increase in LD50 for BPDE in vitro when compared to control-transfected clone G3. This increase in protection, however, did not prevent the formation of BP-induced tumors in vivo.
Boucher
D M
DM
Department of Pathology and Pediatrics, Northwestern University Medical School, Chicago, IL 60614, USA.
Iannaccone
P M
PM
D016475:3T3 Cells; D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; D000818:Animals; D002273:Carcinogens; D005982:Glutathione Transferase / Q000096:biosynthesis* / Q000627:therapeutic use; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis* / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000139:chemically induced* / Q000201:enzymology* / Q000517:prevention & control; D013237:Stereoisomerism; D014162:Transfection / Q000187:drug effects
D002273:Carcinogens; D007527:Isoenzymes; D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; D005982:Glutathione Transferase