Inhibitory Effects of Benzyl Isothiocyanate and Benzyl Thiocyanate on Diethylnitrosamine‐induced Hepatocarcinogenesis in Rats

Abstract

The effects of two aromatic thiocyanates, benzyl isothiocyanate (BITC) and benzyl thiocyanate (BTC), on diethylnitrosamine (DEN)‐induced hepatocarcinogenesis were examined in rats. A total of 108 male ACI/N rats, 5 weeks old, were divided into 6 groups (18 rats in each). Group 1 was given a single i.p, injection of DEN (200 mg/kg body weight) one week after the start of the experiment and then kept on the basal diet until the end of the experiment (1 year). Groups 2 and 3 were treated with DEN and received dietary BITC (100 ppm) or BTC (100 ppm), respectively, throughout the experimental duration. Groups 4 and 5 were not given the carcinogen and were fed the diet containing BITC or BTC, respectively. Group 6 was kept on the basal diet alone and served as a control. Liver neoplasms were seen in Groups 1, 2 and 3. Incidence and average number of liver neoplasms in Group 2 were significantly smaller than in Group 1 (P<0.0005 and P<0.001, respectively). The incidence of liver neoplasms in Group 3 was slightly lower than in Group 1, although the difference was not statistically significant. The numbers of glutathione S‐transferase placental form (GST‐P)‐positive foci in Group 2 and γ‐glutarnyltranspepridase (GGT)‐positive foci in Groups 2 and 3 were significantly smaller than those in Group 1 (P<0.001). The average and unit areas of GST‐P‐ or GGT‐positive foci in Group 2 or 3 were also significantly smaller than those in Group 1 (P<0.05). These results suggest that BITC and BTC are chemopreventive agents for DEN‐induced liver tumorigenesis.