Evidence for an Adenoma-carcinoma Sequence in Dimethylhydrazine-induced Neoplasms of Rat Intestinal Epithelium

Carcinogen-induced primary intestinal adenocarcinomas serve as a useful animal model for human colonic adenocarcinomas. Although striking similarities between this model and the human disease state exist, there are also troublesome discrepancies-a major one being the reported lack of an adenoma-carcinoma sequence in the experimental model. However, the original morphologic descriptions of these experimental neoplasms predated the development of presently accepted morphologic criteria that have been used to describe the adenoma-carcinoma sequence in humans. Therefore, the authors reevaluated the structural evolution of dimethylhydrazine-induced rat intestinal neoplasms, using the same criteria that were recently applied to evaluate human colonic adenocarcinomas. Such an approach shows that many dimethylhydrazine-induced intestinal adenocarcinomas have peripheral foci of adenomatous epithelium associated with them. In addition, the frequency of this association correlates inversely (P less than .001) with the depth of invasion. These findings are comparable to those which, in humans, have been used as evidence supporting the adenoma-carcinoma sequence. Thus, when assessed with equivalent criteria, dimethylhydrazine-induced intestinal adenocarcinomas appear to be similar, not dissimilar, to human colonic adenocarcinomas in their structural evolution. These data suggest that, at least in part, dimethylhydrazine-induced intestinal adenocarcinomas arise in foci of preexisting adenomatous epithelium.