Abstract:
: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).
journal_name
Cancer Lettjournal_title
Cancer lettersauthors
Xu M,Dashwood RHdoi
10.1016/s0304-3835(99)00121-4keywords:
subject
Has Abstractpub_date
1999-09-01 00:00:00pages
179-83issue
2eissn
0304-3835issn
1872-7980pii
S0304383599001214journal_volume
143pub_type
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