TitleChemoprevention studies of heterocyclic amine-induced colon carcinogenesis.
Publication TypeJournal Article
Year of Publication1999
AuthorsXu M, Dashwood RH
JournalCancer Lett
Date Published1999 Sep 01
KeywordsAnimals, Anticarcinogenic Agents, Carcinogens, Catechin, Chlorophyllides, Colon, Colonic Neoplasms, Drug Antagonism, Imidazoles, Indoles, Linoleic Acid, Precancerous Conditions, Quinolines, Rats, Rats, Inbred F344

The cooking of meat and fish produces heterocyclic amine mutagens, including 2-amino-1-methyl-6-phenylimidazo[4,5b]pyridine (PhIP) and 2-amino-3-methylimidazo[4,5-f]quinoline (IQ). Chronic administration of PhIP or IQ to the F344 rat induces tumors at several sites, including adenocarcinomas of the colon, and short-term treatment leads to the formation of colonic aberrant crypt foci (ACF). We have used these end-points to identify potential chemopreventive agents that might be effective against heterocyclic amine colon carcinogens. Typically, IQ or PhIP were administered to groups of 10-15 rats by oral gavage on alternating days in weeks 3 and 4, and ACF were scored after 8, 12, or 16 weeks or tumors were detected at 52 weeks. To distinguish between 'blocking' and 'suppressing' agents, potential inhibitors were administered during the initiation or post-initiation phases, respectively, and subsequent studies focused on the inhibitory mechanisms. Among the most effective inhibitors identified to date, and their major mechanisms, were the following: chlorophyllin (molecular complex formation); indole-3-carbinol (inhibition and induction of cytochromes P450 and phase II enzymes); green and black tea catechins (induction of UDP-glucuronosyl transferase, inhibition of NADPH-cytochrome P450 reductase, scavenging of reactive intermediates); and conjugated linoleic acids (inhibition of cytochrome P450 and prostaglandin H synthase).

Alternate JournalCancer Lett.
PubMed ID10503900
Grant ListR01 CA065525-06A1 / CA / NCI NIH HHS / United States
CA65525 / CA / NCI NIH HHS / United States