The role of aberrant crypt foci induced by the two heterocyclic amines 2-amino-3-methyl-imidazo[4,5-f]quinoline (IQ) and 2-amino-1-methyl-6-phenyl-imidazo[4,5-b]pyridine (PhIP) in the development of colon cancer in mice.
Aberrant crypt foci (ACF) have recently been identified as early putative preneoplastic lesions which appear in the colons of experimental animals treated with colon carcinogens. In a recent study the two heterocyclic amines, 2-amino-3-methyl-imidazo[4,5-f]quinoline (IQ) and 2-amino-1-methyl-6-phenyl-imidazo[4,5-b]pyridine (PhIP) were shown to be able to induce ACF in the colon of mice after, respectively, 4 and 10 weeks of exposure. In spite of the induction of ACF in colon of mice, IQ and PhIP have not been found to have colon as target organ in carcinogenicity studies. Therefore, one may question that ACF induced by IQ and PhIP in mice represent early stages of colon cancer. In order to investigate the possible role of PhIP- and IQ-induced aberrant crypt foci in the development of colon cancer in mice, colons from mice participating in other IQ- and PhIP-studies of much longer duration were analyzed for ACF. The results of these studies showed that the number of ACF increased statistically significantly over time, and that the small ACF were predominant (95-100%) at all time-points. In conclusion, this finding suggests that the detection of a high number of ACF with low crypt multiplicity (1-3 AC/Focus) in mice colon after IQ- or PhIP-treatment is not indicative for the end-point colon cancer, and thus supports the hypothesis that only the presence of a high number of ACF with high crypt multiplicity is predictive for tumor outcome.
Kristiansen
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Institute of Toxicology, National Food Agency, Søborg, Denmark. ek@1st.min.dk
D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D003106:Colon / Q000187:drug effects* / Q000473:pathology; D003110:Colonic Neoplasms / Q000139:chemically induced* / Q000473:pathology; D005260:Female; D007093:Imidazoles / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000139:chemically induced / Q000473:pathology; D011230:Precancerous Conditions / Q000139:chemically induced* / Q000473:pathology; D011804:Quinolines / Q000633:toxicity*
D002273:Carcinogens; D007093:Imidazoles; D011804:Quinolines; C071417:2-nitro-3-methylimidazo(4,5-f)quinoline; C049584:2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine