Histogenesis and growth pattern of 1,2-dimethylhydrazine-induced rat colon adenocarcinoma.

Abstract

The histogenesis and growth pattern of colon adenocarcinoma have been studied using 74 BD IX rats given 20 mg 1,2-dimethylhydrazine hydrochloride per kg, s.c., weekly from Day 11 to their 24th week and serially sacrificed with controls. Modifications in DNA synthesis activity and early tumor changes were sought on histological and radioautographic preparations of normal-appearing colon mucosa. All visible colorectal tumors were analyzed for size, site, and pathology. Chronic dimethylhydrazine treatments resulted in a simultaneous increase in the number of both total and tritiated thymidine-labeled cells in the glands of Lieberkühn. In addition, microscopic carcinomatous foci were observed after the 15th week, and the first macroscopic adenocarcinomas appeared in 24-week-old animals. Their number thereafter exponentially increased with time. A total of 252 macroscopic tumors were obtained, of which 14 were classified as signet ring cell carcinomas and 238 as adenocarcinomas. Among the latter, local invasion could be documented in 230, including the smallest. No benign polypcancer sequence could be demonstrated in this material. The average growth pattern of those adenocarcinomas could be adequately described by a Gompertz curve, with a short initial doubling time (e.g., 7.5 days in 1.0-cu mm tumors) that progressively increases with time (e.g., 59.6 days in 5000-cu mm tumors).