Enhancing effects of organosulfur compounds from garlic and onions on hepatocarcinogenesis in rats: association with increased cell proliferation and elevated ornithine decarboxylase activity.

Four organosulfur compounds from garlic and onions were examined for modifying effects on diethylnitrosamine (DEN)-induced neoplasia of the liver in male F344 rats using the medium-term bioassay system based on the two-step model of hepatocarcinogenesis. Carcinogenic potential was scored by comparing the numbers and areas per cm2 of induced glutathione S-transferase placental form-positive foci. Isothiocyanic acid isobutyl ester (IAIE), dipropyl trisulfide (DPT), and allyl mercapton (AM) exerted enhancing effects on their development, while dimethyl trisulfide also tended to increase them. To investigate possible mechanisms of the modifying influence, sequential changes in ornithine decarboxylase activity (ODC) over 24 h were measured in AM-treated liver tissue without prior DEN initiation. The activity started to increase by 4 h after AM-treatment, and reached maximum at 16 h, compared to controls. Spermidine/spermine N1-acetyltransferase activity was not significantly changed. An increase in proliferating cell nuclear antigen-positive cells followed the elevation of ODC activity. These results suggest that IAIE, DPT, and AM promote rat hepatocarcinogenesis and their promoting effect might be caused by increased cell proliferation with increased polyamine biosynthesis. In evaluating relationships between diet and cancer, it is thus appropriate to consider not only a possible protective role of garlic and onions, but also enhancing effects.