title: Modifying effects of liver tumor promotion in rats subjected to co-administration of indole-3-carbinol and phenobarbital.
abstract: Indole-3-carbinol (I3C) and phenobarbital (PB) are cytochrome P450 (CYP) 1A and CYP2B inducers, respectively, and have liver tumor-promoting effects in rats. In this study, we investigated the modifying effects on tumor promotion by I3C and PB co-administration. Six-week-old male F344 rats received a single intraperitoneal injection of N-diethylnitrosamine for initiation treatment. Two weeks after the initiation, rats were given no tumor-promoting agents (DEN alone), I3C (2,500 or 5,000 ppm in diet), PB (60 or 120 ppm in drinking water), or 2,500 ppm I3C + 60 ppm PB for 6 weeks. One week after the I3C/PB treatments, all animals underwent a two-thirds partial hepatectomy. The number and area of liver cell foci positive for glutathione S-transferase placental form (GST-P(+) foci) were not significantly fluctuated in the PB+I3C group in the isoadditive statistical model. On the contrary, the mRNA levels of Cyp2b1/2 and Nqo1 were suppressed and enhanced, respectively, in the PB+I3C group in the isoadditive model, but there was no enhancement in the microsomal reactive oxygen species (ROS) production, thiobarbituric acid-reactive substance levels, and Ki-67(+) cell ratio in this group. The results suggest that the co-administration of I3C and PB causes no modifying effects in liver tumor promotion in rats.
authors.affiliation: Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology.
authors.forename: Risa
authors.initials: R
authors.lastname: Segawa
authors.forename: Hitomi
authors.initials: H
authors.lastname: Hayashi
authors.forename: Reiko
authors.initials: R
authors.lastname: Morita
authors.forename: Takashi
authors.initials: T
authors.lastname: Ogawa
authors.forename: Norifumi
authors.initials: N
authors.lastname: Takimoto
authors.forename: Shintaro
authors.initials: S
authors.lastname: Hara
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Suzuki
authors.forename: Makoto
authors.initials: M
authors.lastname: Shibutani
authors.forename: Kunitoshi
authors.initials: K
authors.lastname: Mitsumori
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002273:Carcinogens; D019362:Cytochrome P-450 CYP2B1 / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004052:Diethylnitrosamine; D004790:Enzyme Induction / Q000187:drug effects; D005982:Glutathione Transferase / Q000378:metabolism; D007211:Indoles / Q000008:administration & dosage / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000139:chemically induced* / Q000473:pathology*; D008297:Male; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism; D010634:Phenobarbital / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D016588:Anticarcinogenic Agents; D002273:Carcinogens; D007211:Indoles; D004052:Diethylnitrosamine; D003577:Cytochrome P-450 Enzyme System; C016517:indole-3-carbinol; D019362:Cytochrome P-450 CYP2B1; D016660:NAD(P)H Dehydrogenase (Quinone); C507703:NQO1 protein, rat; D005982:Glutathione Transferase; D010634:Phenobarbital