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

Int J Cancer. 1997 Dec 10;73(6):897-902. doi: 10.1002/(sici)1097-0215(19971210)73:6<897::aid-ijc23>;2-0.


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 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)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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Allyl Compounds / isolation & purification
  • Allyl Compounds / therapeutic use
  • Animals
  • Anticarcinogenic Agents / isolation & purification
  • Anticarcinogenic Agents / therapeutic use*
  • Benzo(a)pyrene / toxicity*
  • Biological Assay / economics
  • Biological Assay / methods
  • Chromatography, High Pressure Liquid
  • Disulfides / isolation & purification
  • Disulfides / therapeutic use
  • Enzyme Induction
  • Female
  • Garlic / chemistry
  • Glutathione S-Transferase pi
  • Glutathione Transferase / biosynthesis*
  • Glutathione Transferase / metabolism
  • Isoenzymes / biosynthesis*
  • Isoenzymes / metabolism
  • Liver / enzymology
  • Mice
  • Mice, Inbred A
  • Plants, Medicinal
  • Propane / analogs & derivatives
  • Propane / isolation & purification
  • Propane / therapeutic use
  • Regression Analysis
  • Stomach / enzymology
  • Stomach Neoplasms / chemically induced
  • Stomach Neoplasms / enzymology
  • Stomach Neoplasms / prevention & control*
  • Sulfides / isolation & purification
  • Sulfides / therapeutic use*
  • Treatment Outcome


  • Allyl Compounds
  • Anticarcinogenic Agents
  • Disulfides
  • Isoenzymes
  • Sulfides
  • diallyl trisulfide
  • Benzo(a)pyrene
  • diallyl disulfide
  • allyl sulfide
  • Glutathione S-Transferase pi
  • Glutathione Transferase
  • Gstp1 protein, mouse
  • n-propyl disulfide
  • dipropyl sulfide
  • Propane