Changes in the Intestinal Microflora in Association with Colon Tumorigenesis in Rats Treated with 1,2‐Dimethylhydrazine Hydrochloride

Abstract

The present study was undertaken to determine whether the intestinal microflora change during the tumorigenic process in the colon of rats treated with 1,2-dimethylhydrazone (DMH), and to compare the intestinal microflora of rats with colon tumors induced by DMH with that of rats with gastric tumors induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). When compared with those in the control animals, the numbers of streptococci and bacteroidaceae were moderately increased in the intestinal tract of DMH-treated rats before the development of visible intestinal tumors. The DMH-treated rats bearing small intestinal and colonic tumors were found to have markedly increased numbers of enterobacteriaceae, Clostridium perfringens, streptococci, bacteroidaceae, and bifidobacteria. In DMH-induction the overgrowth of enterobacteriaceae and/or C. perfringens was found to correlate with the size and number of tumors in both the small intestine and colon. The increased number of streptococci in the DMH-treated rats was principally due to an increase in the number of the streptococci which did not reduce triphenyltetrazolium chloride (TTC). On the other hand, in the rats with gastric tumors induced by MNNG the numbers of enterobacteriaceae and TTC-reducing streptococci were remarkably increased in the intestinal tract of only the debilitated animals, and Pseudomonas aeruginosa was detected in all of them. The number of anaerobic grampositive cocci was significantly but not remarkably increased in the gastric tumorbearing rats compared with the controls. These results indicate that the intestinal microflora of rats may change depending on the gastrointestinal site where tumors develop and the degree of malignancy in tumorigenesis.The intestinal microftora is considered to play an important role in colon carcinogenesis in human because of the production of carcinogenic and cocarcinogenic substances by the metabolic activity of the intestinal bacteria (2,3,6,8, 11,16,18), and the fecal microftora of patients with large bowel cancers has been investigated by several workers (1,(6)(7)(8). In an experimental model for human colon cancer, the incidence of colon cancer induced by 1,2-dimethylhydrazine (DMH) in rats was also related to bacterial metabolic activity in the intestine which may be changed by diets (4,5,(12)(13)(14). Moreover, DMH treatment per se was shown to increase the bacterial modification of bile acids and intestinal ammonia 485