CHEMOPREVENTIVE PROPERTIES OF INDOLE-3-CARBINOL (I3C) - INHIBITION OFDNA ADDUCT FORMATION OF THE DIETARY CARCINOGEN, 2-AMINO-1-METHYL-6-PHENYLIMIDAZO [4,5-B]PYRIDINE (PHIP), IN FEMALE F344 RATS

Indole-3-carbinol (13C), a naturally occurring inhibitor of experiment al carcinogenesis, was evaluated for its possible inhibitory effect on DNA-adduct formation of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridi ne (PhlP), a dietary mutagen, in female F344 rats. PhlP is a mammary c arcinogen 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. PhlP (0.04% , w/w) was added to the diet from days 15 through 42. Animals were kil led on days 43 and 58. DNA isolated from mammary epithelial cells (MEC s), colon, liver, and white blood cells (WBCs) was analyzed for PhlP-D NA adducts by P-32-postlabeling assays. On day 43, adduct levels of th e group receiving 0.1% dietary 13C decreased in MECs (91.9%), colon (6 7.2%), liver (69.2%), and WBCs (82.3%). On day 58, DNA adduct formatio n was inhibited in the colon (81.3-82.2%) at both dietary 13C concentr ations, and in liver (46.8%) only in the animals fed 0.1% 13C. When in corporated in the diet after exposure to dietary PhlP (0.04% for 2 wee ks), 13C (0.1%) had no effect on the rate of removal of PhlP-DNA adduc ts over the next 28 days. It is concluded that dietary 13C inhibits Ph lP-DNA adduct formation in the female F344 rat but does not affect add uct removal. 13C may be a promising chemopreventive agent in PhlP-indu ced carcinogenesis in rats. (C) 1998 Wiley-Liss, Inc.