Overexpression of human glutathione S-transferase π protects NIH 3T3 cells against (±)anti BPDE cytotoxicity but not tumor formation

In order to explore the protective function of human glutathione S-transferase π (GST-π) 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 car cinogen benzo(a)pyrene (BP) to induce tumor formation. The human GST-π cDNA under the control of the murine α₂(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-π 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.