Abstract
It has been well known that the oral administration of sulfated polysaccharide, including degraded carrageenan (d-CGN) and amylopectin sulfate (APS), induces ulcerative colitis in various laboratory animals. Furthermore, prolonged oral administration of d-CGN is carcinogenic to the colorectum of the rat. D-CGN first induces ulcerative lesions, secondarily squamous metaplasia and finally tumors. However, there has been no report concerning the carcinogenicity of and colorectal lesions caused by APS. The effects of the oral administration of APS on rats were studied.
After F344 rats were fed diets containing APS (5 % W/W) for three, six or nine months, all the animals were fed a regular diet and killed 12 months after the initial administration. APS induced adenoma and adenocarcinoma in the colorectum of the rats. The incidence of the tumors was two out of 20 rats (10%) in the three-month group (group I), nine out of 20 rats (45%) in the six-month group (group II) and 12 out of 20 rats (60%) in the nine-month group (group III). All the tumors were protuberant. The sessile lesions were smaller than the pedunculated type, and the former had a tendency to submucosal carcinomatous invasion. In the control group, no colorectal tumors were present. Squamous metaplasia of the colorectum persisted in all the experimental rats. And hyperplasia of the squamous epithelium was not prominent. The length of the squamous metaplasia from the dentate line was 2.22 ア 0.50 cm in group I, 3.49 ア 0.4. cm in group II, 4.98 ア 0.85 cm in group III, showing statistically significant differences from one other (P < 0.01). On the other hand, foamy macrophages containing amylopectin sulfate remained in such areas as the colorectal mucosal lamina propria, colorectal submucosa, and regional lymph nodes. There were some macrophages in the liver and spleen.
APS already induced epithelial degeneration or superficial erosions in the colon and rectum one week after initiation of the administration. The epithelial degeneration was found electron microscopically on the first or third day of the administration. The colorectal squamous metaplasia followed after two weeks of the administration. The mutagenicity Ames test of APS showed negative results.
