INDUCTION OF GLUTATHIONE-S-TRANSFERASE-PI 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 th at the induction of glutathione (GSH) S-transferase pi (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)pyre ne (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 fo restomach of female A/J mice in the detoxification of the ultimate car cinogenic metabolite of BP, hydroxy-9,10-oxy-7,8,9,10-tetrahydrobenzo( a)pyrene [(+)-anti-BPDE]; and 2) a positive correlation between the in duction of hepatic and forestomach mGSTP1-1 by 5 naturally occurring o rganosulfides (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 detoxifi cation 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 effe cts of OSCs against BP-induced forestomach neoplasia revealed a good c orrelation between their chemo-preventive efficacy and their ability t o induce mGSTP1-1 expression in the liver (r = -0.89; p < 0.05) as wel l as in the forestomach (r = -0.97; p < 0.05). Our results suggest tha t the induction of mGSTP1-1 may be a reliable marker for evaluating th e efficacy of potential inhibitors of BP-induced cancer in a murine mo del. (C) 1997 Wiley-Liss, Inc.