THE ROLE OF ABERRANT CRYPT FOCI INDUCED BY THE 2 HETEROCYCLIC AMINES 2-AMINO-3-METHYL-IMIDAZO[4,5-F]QUINOLLNE (IQ) AND 2-AMINO-1-METHYL-6-PHENYL-IMIDAZO[4,5-B]PYRIDINE (PHIP) IN THE DEVELOPMENT OF COLON-CANCERIN MICE

Aberrant crypt foci (ACF) have recently been identified as early putat ive preneoplastic lesions which appear in the colons of experimental a nimals treated with colon carcinogens. In a recent study the two heter ocyclic amines, 2-amino-3-methyl-imidazo[4,5-f]quinoline (IQ) and 2-am ino-1-methyl-6-phenyl-imidazo[4,5-b]pyridine (PhIP) were shown to be a ble to induce ACF in the colon of mice after, respectively, 4 and 10 w eeks of exposure. In spite of the induction of ACF in colon of mice, I Q and PhIP have not been found to have colon as target organ in carcin ogenicity studies. Therefore, one may question that ACF induced by IQ and PhIP in mice represent early stages of colon cancer. In order to i nvestigate the possible role of PhIP- and IQ-induced aberrant crypt fo ci in the development of colon cancer in mice, colons from mice partic ipating in other IQ- and PhIP-studies of much longer duration were ana lyzed for ACF. The results of these studies showed that the number of ACF increased statistically significantly over time, and that the smal l ACF were predominant (95-100%) at all time-points. In conclusion, th is finding suggests that the detection of a high number of ACF with lo w crypt multiplicity (1-3 AC/Focus) in mice colon after IQ- or PhIP-tr eatment is not indicative for the end-point colon cancer, and thus sup ports the hypothesis that only the presence of a high number of ACF wi th high crypt multiplicity is predictive for tumor outcome.