Induction of glutathione S‐transferase π as a bioassay for the evaluation of potency of inhibitors of benzo(a)pyrene‐induced cancer in a murine model

There is a growing need for short‐term and cost‐effective bioassay to assess the efficacy of potential chemo‐preventive agents. We report that the induction of glutathione (GSH) S‐transferase π (mGSTP1‐1) by a chemo‐preventive agent can be used as a reliable marker to assess its efficacy in retarding chemical carcinogenesis induced by benzo(a)pyrene (BP), which is a widespread environmental pollutant and believed to be a risk factor in human chemical carcinogenesis. This conclusion is based on 1) the relative contribution of mGSTP1‐1 of the liver and forestomach of female A/J mice in the detoxification of the ultimate carcinogenic metabolite of BP, (+)‐anti‐7,8‐dihydroxy‐9,10‐oxy‐7,8,9,10‐ tetrahydrobenzo(a)pyrene [(+)‐anti‐BPDE]; and 2) a positive correlation between the induction of hepatic and forestomach mGSTP1‐1 by 5 naturally occurring organosulfides (OSCs) from garlic (diallyl sulfide, diallyl disulfide, diallyl trisulfide, dipropyl sulfide and dipropyl disulfide) and their effectiveness in preventing BP‐induced forestomach neoplasia in mice. In the liver, the combined contribution of other GSTs in the detoxification of (+)‐anti‐BPDE was far less than the contribution of mGSTP1‐1 alone. Likewise, in the forestomach, the contribution of mGSTP1‐1 far exceeded the combined contribution of other GSTs. Studies on the effects of OSCs against BP‐induced forestomach neoplasia revealed a good correlation between their chemo‐preventive efficacy and their ability to induce mGSTP1‐1 expression in the liver (r = −0.89; p < 0.05) as well as in the forestomach (r = −0.97; p < 0.05). Our results suggest that the induction of mGSTP1‐1 may be a reliable marker for evaluating the efficacy of potential inhibitors of BP‐induced cancer in a murine model. Int. J. Cancer 73:897–902, 1997. © 1997 Wiley‐Liss, Inc.