Long term dietary indole-3-carbinol inhibits diethylnitrosamine-initiated hepatocarcinogenesis in the infant mouse model

Abstract

Indole-3-carbinol (I3C), a natural component from cruciferous vegetables, has been demonstrated to be a modulator of carcinogenesis in various animal models. Along with the promising perspectives of I3C as a possible chemopreventive agent for human breast cancer, some concerns have been raised regarding the tumor-promotional potency of this compound in other target organs. In this study we examined the hepatic tumor-modulatory properties of I3C fed to C57BL/6J mice, initiated with diethylnitrosamine (DEN). Infant male mice were initiated with 0, 2 or 5 mg/kg DEN (i.p. injection) at 15 days of age. Mice were weaned 9 days later and immediately put on AIN76A semipurified diet (with no antioxidants) containing 0 or 0.15% (1500 ppm) I3C. In addition, at the age of 2 months, one group of mice initiated with 2 mg/kg DEN was injected i.p. with a single dose (20 mg/kg) of 3,4,5,3′,4′,5′-hexachlorobiphenyl (HCB), to serve as a positive control group for promotion. Mice were sampled for hepatic tumors at the age of 6 or 8 months. Each sampled group contained 11–12 mice except the HCB group (nine animals). After 8 months, there was a statistically significant ( P < 0.0005) inhibition of hepatocarcinogenesis observed for I3C-fed animals initiated with the high dose of DEN. A single injection of HCB at 2 months of age significantly ( P = 0.0003) enhanced hepatocarcinogenesis in mice initiated with 2 mg/kg DEN. There was no statistically significant difference between groups sampled at 6 months of age. Our observations indicate that long term administration of I3C in the diet inhibits DEN-initiated hepatocarcinogenesis in the infant mouse model.