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 occurring compound found in cruciferous vegetables, on neoplastic development was assessed using a rat medium-term multiorgan carcinogenesis model. One-hundred male Sprague-Dawley (SD) rats were randomly divided into three groups and sequentially treated with diethylnitrosamine (DEN; 100 mg/kg b.w., 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-propyl-nitrosamine (DHPN; 0.1% in the drinking water during weeks 1 and 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, followed 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 (no./cm2) and area (mm2/cm2) of glutathione S-transferase placental form (GST-P)-positive liver cell foci assessed at week 24 of the experiment (P<0.01, 0.001). The incidence of hepatocellular adenomas in the DMD and I3C group at week 52 showed a tendency for elevation as compared to the DMD alone group, but this was not statistically significant. The thyroid gland tumour incidences in the DMD and I3C groups were significantly increased compared with the DMD alone group values at week 52 (P<0.01). In conclusion, I3C enhanced liver and thyroid gland neoplastic development when given during the promotion stage in the present rat medium-term multiorgan carcinogenesis model.
Kim
D J
DJ
Chemotherapy Division, National Cancer Centre Research Institute, Chuo-ku, Tokyo, Japan.
Han
B S
BS
Ahn
B
B
Hasegawa
R
R
Shirai
T
T
Ito
N
N
Tsuda
H
H
D000230:Adenocarcinoma / Q000139:chemically induced; D000236:Adenoma / Q000139:chemically induced; D000818:Animals; D016588:Anticarcinogenic Agents / Q000009:adverse effects*; D015197:Carcinogenicity Tests; D002273:Carcinogens; D004052:Diethylnitrosamine; D004357:Drug Synergism; D007211:Indoles / Q000009:adverse effects*; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced*; D008297:Male; D008770:Methylnitrosourea; D009374:Neoplasms, Experimental / Q000139:chemically induced; D009602:Nitrosamines; D051381:Rats; D017207:Rats, Sprague-Dawley; D013964:Thyroid Neoplasms / Q000139:chemically induced*
D016588:Anticarcinogenic Agents; D002273:Carcinogens; D007211:Indoles; D009602:Nitrosamines; D004052:Diethylnitrosamine; C012457:diisopropanolnitrosamine; D008770:Methylnitrosourea; C016517:indole-3-carbinol