It has been reported that several naturally occurring and related synthetic organosulfur compounds exert chemopreventive effects in several target organs in rodent models. The chemopreventive actions of 40 and 80% maximum tolerated doses (MTD) of organosulfur compounds, namely
anethole trithione,
diallyl disulfide,
N-acetylcysteine, and
taurine, administered in AIN-76A diet, on
azoxymethane (AOM)-induced
neoplasia were investigated in male F344 rats. Also, the effects of these agents on the activities of phase II
enzymes, namely
glutathione S-transferase (GST),
NAD(P)H-dependent
quinone reductase, and
UDP-glucuronosyl
transferase, in the liver and colonic mucosa and
tumors were assessed. The MTD levels of
anethole trithione,
diallyl disulfide,
N-acetylcysteine, and
taurine were determined in male F344 rats and found to be 250, 250, 1500, and 1500 ppm, respectively. At 5 weeks of age, animals were fed the control diet (AIN-76A) or experimental diets containing 40 or 80% MTD levels of each test agent. All animals in each group, except those allotted for vehicle (saline) treatment, were administered AOM s.c. at a dose rate of 15 mg/kg
body weight once weekly for 2 weeks. All animals were necropsied during week 52 after the second AOM injection. Colonic mucosal and
tumor and liver
enzyme activities were measured in animals fed 80% MTD levels of each test agent. Colon
tumors were subjected to histopathological evaluation and classified as invasive or noninvasive
adenocarcinomas. Colon
tumor incidence (percentage of animals with
tumors) and
tumor multiplicity (
tumors/animal) were compared among various dietary groups. The results indicated that administration of 200 ppm (80% MTD)
anethole trithione significantly inhibited the incidence and multiplicity of both invasive and noninvasive
adenocarcinomas, whereas feeding of 100 ppm (40% MTD)
anethole trithione or 100 (40% MTD) or 200 ppm (80% MTD)
diallyl disulfide suppressed only invasive
adenocarcinomas of the colon. Although diets containing
N-acetylcysteine and
taurine inhibited colon
tumor multiplicity, the effect was somewhat marginal. GST,
NAD-(P)H-dependent
quinone reductase, and
UDP-glucuronosyl
transferase activities in colonic mucosa and
tumor and liver were significantly elevated in animals fed
anethole trithione or
diallyl disulfide, compared to those fed the control diet.
N-Acetylcysteine and
taurine slightly but significantly increased only the GST activity in the liver. Although other mechanisms are not excluded, inhibition of AOM-induced colon
carcinogenesis by
anethole trithione and
diallyl disulfide may be associated, in part, with increased activities of phase II
enzymes such as GST,
NAD(P)H-dependent
quinone reductase, and
UDP-glucuronosyl
transferase in the liver and colon.