Dose-response studies of the effect of dietary butylated hydroxyanisole on colon carcinogenesis induced by methylazoxymethanol acetate in female CF1 mice.
The effect of dietary butylated hydroxyanisole (BHA) on methylazoxymethanol acetate [(MAM AC) CAS: 592-62-1; methyl-ONN-azoxy)methanol acetate]-induced intestinal carcinogenesis was studied in female CF1 mice. BHA was added at levels of 0, 0.03, 0.1, 0.3, and 0.6% to the NIH-07 open-formula diet and at 0 and 0.6% to the AIN-76 semipurified diet and fed to mice, starting at 5 weeks of age until termination of the experiment. At 7 weeks of age, all animals except the vehicle-treated controls were given ip injections of MAM AC (15 mg/kg body wt for four times in 11 days for the low-dose group: total dose, 60 mg/kg body; 15 mg/kg body wt for eight times in 22 days for the high-dose group: total dose, 120 mg/kg body wt). With a low dose of carcinogen, the lung tumor incidence was inhibited in mice fed the NIH-07 diet containing 0.03-0.6% BHA and the AIN-76 diet containing 0.6% BHA compared to lung tumor incidence in those fed the diets without BHA; with a high dose of carcinogen, the inhibition was observed in mice fed the NIH-07 diet containing 0.1-0.6% BHA. Colon tumor incidence and colon tumor multiplicity (number of tumors per animal and number of tumors per tumor-bearing animal, respectively) were lower in mice fed the NIH-07 diets with 0.03-0.6% BHA or fed the AIN-76 diet with 0.6% BHA, as well as treated with a low dose of carcinogen, than in animals fed no BHA; with a high dose of carcinogen, colon tumor multiplicity and colon tumor incidence were inhibited in animals fed the NIH-07 diet containing 0.1-0.6% BHA. Consumption of the NIH-07 diets containing 0.03-0.6% BHA resulted in increased glutathione transferase activity of liver and small intestinal and colon mucosae in a dose-related manner.
D000818:Animals; D000840:Anisoles / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D002083:Butylated Hydroxyanisole / Q000494:pharmacology* / Q000633:toxicity; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000517:prevention & control*; D004032:Diet; D004305:Dose-Response Relationship, Drug; D005260:Female; D005982:Glutathione Transferase / Q000032:analysis; D008175:Lung Neoplasms / Q000517:prevention & control; D008746:Methylazoxymethanol Acetate / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains
D000840:Anisoles; D002083:Butylated Hydroxyanisole; D008746:Methylazoxymethanol Acetate; D005982:Glutathione Transferase