The incidence of aberrant crypt foci and colonic carcinoma in dimethylhydrazine-treated rats varies in a site-specific manner and depends on tumor histology

Abstract

In an attempt to demonstrate the relationship between aberrant crypt foci (ACF) and subsequent colonic neoplasms, we investigated the distribution of ACF in the dimethylhydrazine (DMH) model of colonic carcinogenesis in the rat. DMH was given to male Wistar rats by s.c. injection in a dosage of 15 mg/kg body weight once a week for 19 weeks. As a result, eight poorly differentiated, mucin-secreting carcinomas, two well-differentiated tubular adenocarcinomas, and four adenomas developed in 35 rats autopsied at 24 weeks after the first injection of DMH. The location of each type of tumor was site specific. Poorly differentiated, mucin-secreting carcinomas of signet-ring type occurred only in the proximal colon; the mean location of these lesions was 17.6 +/- 3.8% (SE; range, 0-39%) of the length of the colon. Well-differentiated tubular adenocarcinomas and adenomas developed in the distal colon; the mean location of these lesions was 76.7% +/- 4.9 (SE; range, 60-90%) of the length of the colon. There was a mean number of 276 +/- 29 (SE) ACF per colon; these were present at between 40 and 90% of the colonic length, peaking at 70%. We conclude that ACF are marker lesions for colonic neoplasms, but only in the distal colon where tumors follow the adenoma-carcinoma sequence; this is not so for the proximal colon, where poorly differentiated, mucin-secreting carcinomas are found. These findings suggest that these latter tumors well may arise de novo and indicate that studies that attempt to correlate ACF with subsequent tumor formation must take cognizance, not only of the site, but also of the tumor type.