Dose-related inhibition of aflatoxin B1 induced hepatocarcinogenesis by the phenolic antioxidants, butylated hydroxyanisole and butylated hydroxytoluene

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Abstract
The effect of butylated hydroxyanisole (BHA) or butylated hydroxytoluene (BHT) on the carcinogenicity in rats of aflatoxin B 1 (AFB 1 ) was investigated. AFB 1 was administered by gastric intubation to male F344 rats at 25μg/kg body wt three times a week such that a total dose of 1.5 mg/kg (0.48mmol/kg) body wt was given over a period of 20 weeks and diets containing either 1000 or 6000 p.p.m. BHA or BHT were fed starting one more week before carcinogen, during administration and for one week after cessation. Animals were killed during exposure and at intervals up to 24 weeks after cessation. Liver altered foci and neoplasms were quantified using the exclusion of cellular iron after iron-loading and γ-glutamyl transpeptidase reaction, as well as conventional staining for identification. Exposure to AFB 1 alone induced substancial numbers of altered foci after 20 weeks and at 24 weeks after cessation of exposure, the incidence of hepato-cellular neoplasms was 63%. In the groups receiving BHA or BHT together with AFB 1 the numbers of altered foci were decreased at all time points and at termination, the final incidence of liver cell neoplasms and number of neoplasms peranimal were also reduced in a dose-related manner. Neoplasms in other organs were rare and were not affected by antioxidant treatment, except for a possible reduction of colon cancer. Thus, BHA and BHT inhibited the hepatocarcino-genesis of concurrently administered AFB 1 without shifting the organotropism.

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