Chemopreventive properties of indole-3-carbinol (I3C): inhibition of DNA adduct formation of the dietary carcinogen, 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine (PhIP), in female F344 rats.
Indole-3-carbinol (I3C), a naturally occurring inhibitor of experimental carcinogenesis, was evaluated for its possible inhibitor effect on DNA-adduct formation of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), a dietary mutagen, in female F344 rats. PhIP is a mammary carcinogen in female F344 rats and a colon carcinogen in male F344 rats. Four-week-old animals (4/group) were maintained on powdered AIN-76A diet with or without 13C (0.02% or 0.1%, w/w) for 58 days. PhIP (0.04%, w/w) was added to the diet from days 15 through 42. Animals were killed on days 43 and 58. DNA isolated from mammary epithelial cells (MECs), colon, liver, and white blood cells (WBCs) was analyzed for PhIP-DNA adducts by 32P-postlabeling assays. On day 43, adduct levels of the group receiving 0.1% dietary I3C decreased in MECs (91.9%), colon (67.2%), liver (69.2%), and WBCs (82.3%). On day 58, DNA adduct formation was inhibited in the colon (81.3-82.2%) at both dietary I3C concentrations, and in liver (46.8%) only in the animals fed 0.1% I3C. When incorporated in the diet after exposure to dietary PhIP (0.04% for 2 weeks), 13C (0.1%) had no effect on the rate of removal of PhIP-DNA adducts over the next 28 days. It is concluded that dietary I3C inhibits PhIP-DNA adduct formation in the female F344 rat but does not affect adduct removal. I3C may be a promising chemopreventive agent in PhIP-induced carcinogenesis in rats.
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Department of Pathology, Medical College of Ohio, Toledo 43614-5806, USA.
Smale
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Schut
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D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D002273:Carcinogens / Q000633:toxicity*; D018736:DNA Adducts; D005260:Female; D007093:Imidazoles / Q000633:toxicity*; D007211:Indoles / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344
D016588:Anticarcinogenic Agents; D002273:Carcinogens; D018736:DNA Adducts; D007093:Imidazoles; D007211:Indoles; C049584:2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine; C016517:indole-3-carbinol