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

Xun Hu, Patrick J. Benson, Sanjay K. Srivastava, Hong Xia, Richard J. Bleicher, Howard A. Zaren, Sanjay Awasthi, Yogesh C. Awasthi, Shivendra V. Singh

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Abstract

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 mG- STP1-1 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.

Original languageEnglish (US)
Pages (from-to)897-902
Number of pages6
JournalInternational Journal of Cancer
Volume73
Issue number6
DOIs
StatePublished - Dec 10 1997

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Benzo(a)pyrene
Glutathione Transferase
Biological Assay
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide
Liver
Neoplasms
Carcinogenesis
Environmental Pollutants
Garlic
Costs and Cost Analysis

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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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. / Hu, Xun; Benson, Patrick J.; Srivastava, Sanjay K.; Xia, Hong; Bleicher, Richard J.; Zaren, Howard A.; Awasthi, Sanjay; Awasthi, Yogesh C.; Singh, Shivendra V.

In: International Journal of Cancer, Vol. 73, No. 6, 10.12.1997, p. 897-902.

Research output: Contribution to journalArticle

Hu, Xun ; Benson, Patrick J. ; Srivastava, Sanjay K. ; Xia, Hong ; Bleicher, Richard J. ; Zaren, Howard A. ; Awasthi, Sanjay ; Awasthi, Yogesh C. ; Singh, Shivendra V. / 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. In: International Journal of Cancer. 1997 ; Vol. 73, No. 6. pp. 897-902.
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