Gut‐associated lymphoid tissue and dimethylhydrazine‐induced colorectal carcinoma in the wistar/furth rat

Abstract

Although gut-associated lymphoid tissue in the form of discrete lymphoid patches (LP-GALT) in mammalian intestine in most prominent in the distal ileum, appendix, and, in some species, the cecal appendage, LP-GALT can be found throughout the intestinal tract. LP-GALT appears as single or multiple subepithelial lymphoid follicles covered by a specialized, structurally unique epithelium. In the colon of the Wistar/Furth (W/Fu) rat, LP-GALT appears as aggregates of follicles, or lymphoid patches, that can be detected macroscopically. We studied the relationship between 1,2-dimethylhydrazine- (DMH) induced colon carcinomas and the lymphoid patch associated epithelium in these animals. In addition, we defined the normal distribution of colonic lymphoid patches in both DMH-treated and control rats. Patches were found macroscopically and confirmed by histologic examination at five constant sites: lower pole of cecum, proximal ascending colon, the major colonic flexure, mid descending colon, and the rectosigmoid. There are also the predominant sites of DMH induced carcinomas in W/Fu rats. In 120 DMH-treated animals, 109 colon carcinomas were found. Eight percent were in the lower pole of the cecum, 56% in the proximal ascending colon, 16% at the major flexure, 15% in the mid descending colon, and 5% in the rectosigmoid. Lymphoid patches could often be detected histologically in association with DMH-induced tumors. The depth of tumor invasion was found to correlate inversely with our ability to identify tumor-associated lymphoid patches suggesting that tumors arising at the anatomical sites were lymphoid patches occur progressively destroyed them. Of colon tumors confirmed histologically to be associated with lymphoid patches, 88% were superficial lesions confined to the submucosa and 12% were more extensive but confined to the bowel wall. No lymphoid patches could be found associated with tumors that extended through the bowel wall. Thus, DMH-induced colon carcinomas in W/Fu rats arise at sites containing preexisting LP-GALT with associated specialized epithelium.

Three Pathways of Colonic Carcinogenesis in Rats

“…High frequency of GALT carcinomas in carcinogen-treated rats was first reported by Deasy et al (30), and later confirmed by various authors (31)(32)(33).…”

Updated Histologic Classification of Adenomas and Carcinomas in the Colon of Carcinogen-treated Sprague-Dawley Rats

“…Recently in 215 DMH-treated SD rats, tumours were found to be 1% serrated adenomas, 8% microtubular adenomas, 3% serrated carcinomas and 3% microtubular carcinomas (19 (20). A similar percentage (62%) was subsequently found in DMH-treated SD rats (21).…”

The Histogenesis of the Third Pathway of Colonic Carcinogenesis in Rats

“…In another experiment with DMH-treated rats, it was found that 37% of colonic neoplasias had a subjacent organized lymphoid nodule (10). These findings strongly suggest that carcinomas in rats evolve not only from conventional adenomas (6) and from serrated adenomas (7), but also from mucosa of gut-associated lymphoid tissue (GALT) (8,9). However, the lesions which give rise to GALT carcinomas remain unidentified.…”

“…Years ago, Deasy et al (8) and Rubio et al (9) reported that colonic carcinomas could also evolve in DMH-treated rats from mucosa built with lymphoid aggregates. In another experiment with DMH-treated rats, it was found that 37% of colonic neoplasias had a subjacent organized lymphoid nodule (10).…”