Enhancement of glutathione S-transferase activity of the mouse forestomach by inhibitors of Benzo[a]pyrene-induced neoplasia of the forestomach.
The effects of glutathione S-transferases (GST) activity and acid-soluble sulfhydryl levels of a number of compounds previously investigated for their capacity to inhibit benzo[a]pyrene (BP)-induced neoplasia of the mouse forestomach were determined. Five of the compounds studied increased the GST activity of the forestomach 78-182%. The five compounds were: p-methoxyphenol, 2-tert-butyl-4-hydroxyanisole, coumarin, alpha-angelicalactone, and benzyl isothiocyanate. With the exception of benzyl isothiocyanate. With the exception of benzyl isothiocyanate, these compounds also increased acid-soluble sulfhydryl levels, but to a lesser magnitude. All five chemicals inhibited BP-induced neoplasia of the forestomach. These data indicate that enhancement of the GST activity by an amount of about 75% or greater is associated with a reduced carcinogenic response of the forestomach to BP. The data also suggest that such enhancement might be used as a method of identifying compounds likely to inhibit BP and other carcinogens detoxified in a similar manner. Inasmuch as inhibition of the action of carcinogens may involve mechanisms other than detoxification by GST, the failure to increase GST activity substantially does not rule out the possibility of a compound being an inhibitor.
D000818:Animals; D001564:Benzo(a)pyrene; D001580:Benzopyrenes / Q000037:antagonists & inhibitors*; D002273:Carcinogens; D003374:Coumarins / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D005982:Glutathione Transferase / Q000378:metabolism*; D008658:Inactivation, Metabolic; D007783:Lactones / Q000494:pharmacology; D051379:Mice; D010636:Phenols / Q000494:pharmacology; D013270:Stomach / Q000032:analysis / Q000201:enzymology*; D013274:Stomach Neoplasms / Q000032:analysis / Q000139:chemically induced* / Q000201:enzymology; D013438:Sulfhydryl Compounds / Q000032:analysis; D013861:Thiocyanates / Q000494:pharmacology
D001580:Benzopyrenes; D002273:Carcinogens; D003374:Coumarins; D007783:Lactones; D010636:Phenols; D013438:Sulfhydryl Compounds; D013861:Thiocyanates; D001564:Benzo(a)pyrene; D005982:Glutathione Transferase