Enhancement by Indole-3-Carbinol of Liver and Thyroid Gland Neoplastic Development in a Rat Medium-Term Multiorgan Carcinogenesis Model

The modifying effects of indole-3-carbinol (I3C), a naturally occurring compound in cruciferous vegetables, were assessed using a rat multiorgan carcinogenesis model. One hundred male Sprague-Dawley (SD) rats were divided randomly into three groups. Groups 1 and 2 were sequentially treated with diethylnitrosamine (DEN), N-methyl-N-nitrosourea (MNU), and dihydroxy-di-N-propylnitrosamine (DHPN) for four weeks (DMD treatment) and Group 3 was given treatment without mutagen. Animals of groups 1 and 3 were given a diet containing 0.25% I3C for 20 weeks after the initiation period, followed by a return to the basal diet for 28 weeks, and subgroups were killed at weeks 24 and 52. I3C caused significant increases in both density and area (mm2/ cm2) of liver cell foci positive for glutathione S-transferase placental form, assessed at week 24 of the experiment (P < 0.01, 0.001). The incidence of hepatocellular adenomas in the DMD → I3C group at week 52 similarly tended to be elevated as compared to the initiation only (DMD-alone) group. The incidence of thyroid gland tumors in the DMD → I3C group was significantly increased compared with the DMD-alone group values at week 52 of the experiment (P < 0.01). In conclusion, I3C was shown to enhance liver and thyroid gland neoplastic development when given during the promotion stage in a rat medium-term multiorgan carcinogenesis model.