Large intestinal carcinogenesis. II. Histogenesis and unusual features of low-dose azoxymethane-induced carcinomas in F344 rats.

The histogenesis of large intestinal carcinomas was studied by use of a low dose (2 mg/kg/wk) of azoxymethane [(AOM) CAS: 25843-45-2] administered im to inbred F344 rats. No evidence of benign polyp was seen, and the carcinomas in this model did arise directly from the flat mucosa. In marked contrast to the standard dose (8 mg/kg/wk) studies, low-dose AOM carcinogenesis yielded the following unusual features: a) There was a very high incidence of readily metastasizing mucinous adenocarcinomas that were extremely aggressive and easily transplantable; b) the carcinomas, microscopic and macroscopic, were localized predominantly in the proximal large intestine; c) foci of atypical early neoplastic (or so-called dysplastic) crypts as well as early carcinomas were frequently associated with the lymphoid aggregates in the intestinal wall; d) Paneth cells were commonly seen to be associated with these atypical crypts and/or early carcinomas associated with the lymphoid aggregates; and e) there was a virtual lack of the dilated, distorted, or hyperdistended crypts in noncarcinomatous epithelia. The significance of the lack of dilated, distorted, hyperdistended crypts and the similarity of this finding with the findings in the low incidence of colon cancer in the Japanese population are discussed.