ENHANCEMENT BY INDOLE-3-CARBINOL OF LIVER AND THYROID-GLAND NEOPLASTIC DEVELOPMENT IN A RAT MEDIUM-TERM MULTIORGAN CARCINOGENESIS MODEL

The modification potential of indole-3-carbinol (I3C), a naturally occ urring compound found in cruciferous vegetables, on neoplastic develop ment was assessed using a rat medium-term multiorgan carcinogenesis mo del, One-hundred male Sprague-Dawley (SD) rats were randomly divided i nto three groups and sequentially treated with diethylnitrosamine (DEN ; 100 mg/kg b. cv., a single i.p,), N-methyl-N-nitrosourea (MNU; 20 mg /kg b.w., four times i.p., at days 5, 8, 11 and 14), and dihydroxy-di- N-propylnitrosamine (DHPN; 0.1% in the drinking water during weeks 1 a nd 3) (DMD treatment; groups 1 and 2) or the vehicles alone (group 3) in the first 3-week initiation period. Animals of groups 1 and 3 were then given diet containing 0.25 % I3C from week 4 until week 24, follo wed by a return to basal diet for 28 weeks, and subgroups were killed at weeks 24 and 52, I3C caused significant increases in both number (n o./cm(2)) and area (mm(2)/cm(2)) of glutathione S-transferase placenta l form (GST-P)-positive liver cell foci assessed at week 24 of the exp eriment (P<0.01, 0.001). The incidence of hepatocellular adenomas in t he DMD and I3C group at week 52 showed a tendency for elevation as com pared to the DMD alone group, but this was not statistically significa nt. The thyroid gland tumour incidences in the DMD and I3C groups were significantly increased compared with the DMD alone group values at w eek 52 (P<0.01). In conclusion, I3C enhanced liver and thyroid gland n eoplastic development when given during the promotion stage in the pre sent rat medium-term multiorgan carcinogenesis model.