AZOXYMETHANE-INDUCED COLON TUMORS AND ABERRANT CRYPT FOCI IN MICE OF DIFFERENT GENETIC SUSCEPTIBILITY

Azoxymethane (AOM) is an organotropic colon carcinogen that is commonl y used to induce colon tumors in rodents. Unlike its parent compound, 1,2-dimethylhydrazine (DMH), a tumor susceptibility phenotype in inbre d mice with respect to AOM has not been established. Thus, this study was undertaken to determine whether genetic susceptibility extends to this carcinogen. SWR/J, A/J (both susceptible to DMH carcinogenesis) a nd AKR/J (resistant) mice were treated with 10 mg/kg AOM i.p. once a w eek for 8 weeks. Twenty-five weeks after the initial injection, tumor yield was determined. With a single exception, only SWR/J and A/J mice developed tumors, with a distribution that was limited to the distal colon (16.3 +/- 1.1 and 36.4 +/- 2.4, respectively). The formation of aberrant crypt foci (ACF), putative preneoplastic lesions, was also as sessed in whole-mount colons using Methylene Blue staining. Consistent with tumor multiplicity, the total number of ACF was highest in A/J m ice, followed by SWR/J mice. In addition, A/J mice had a significantly greater number of large ACF (five or more crypts per foci) than the o ther strains. Despite the absence of colon tumors, however, AKR/J mice did develop a significant number of ACF. This finding suggests that A CF in resistant mice are persistent but do not progress to tumors. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.