Long term dietary indole-3-carbinol inhibits diethylnitrosamine-initiated hepatocarcinogenesis in the infant mouse model.
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.
Oganesian
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A
Department of Food Science, and the Marine/Freshwater Biomedical Sciences Center, Oregon State University, Corvallis, 97331-6602, USA.
Hendricks
J D
JD
Williams
D E
DE
D000284:Administration, Oral; D000375:Aging; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000517:prevention & control; D002273:Carcinogens; D004052:Diethylnitrosamine; D005260:Female; D005527:Food, Fortified; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000254:growth & development / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013997:Time Factors
D016588:Anticarcinogenic Agents; D002273:Carcinogens; D007211:Indoles; D004052:Diethylnitrosamine; C016517:indole-3-carbinol