Inhibitory effects of benzyl thiocyanate and benzyl isothiocyanate on methylazoxymethanol acetate-induced intestinal carcinogenesis in rats.

Abstract

The effects of two aromatic thiocyanates, benzyl thiocyanate (BTC) and benzyl isothiocyanate (BITC), on methylazoxymethanol (MAM) acetate-induced intestinal carcinogenesis were examined using female ACI/N rats. Starting at 5 weeks of age, animals were fed diets containing 100 or 400 p.p.m. BTC, 400 p.p.m. BITC or a control diet. At 6 weeks of age, all animals were treated with i.p. injections of MAM acetate (25 mg/kg body wt, once weekly for 3 weeks) or saline. Animals fed experimental diets were changed to the control diet from a week after the last carcinogen treatment. Three groups of animals fed the control diet were switched to 100 p.p.m. BTC, 400 p.p.m. BTC or 400 p.p.m. BITC diet from a week after carcinogen treatment. Animals given the high-dose BTC diet at the initiation and the post-initiation phase showed smaller incidence (5% and 17%) and multiplicity (0.05 +/- 0.21 and 0.17 +/- 0.37) of tumours in small intestine compared with those of rats exposed to the carcinogen alone (61% and 1.06 +/- 1.18). The incidence and multiplicity of tumors in small intestine (21% and 0.32 +/- 0.73) and the incidence of colon tumors of rats given BITC in the initiation phase (47%) were significantly lower than those of animals treated with carcinogen alone (61%, 1.06 +/- 1.18 and 83%). Bromodeoxyuridine labeling indices of the intestinal mucosal cells were measured. The labeling indices were reduced by BTC and BITC exposure at initiation phase in both small intestine and colon. The results of measurement of labeling indices correlated with the decreased tumor incidence and multiplicity in the intestine. These data suggest that BTC and BITC could be promising chemopreventive agents for human intestinal neoplasia.