Studies on experimental colon tumorigenesis in rats. 2. Cell kinetics of the colon epithelium and its relation to histogenesis of colon tumors.

1, 2-Dimethylhydrazine (DMH) was administered to a total of 131 Wister Furth substrain (WF /0) rats 20 times weekly at a dose of 20 mg/kg body weight. The tumors were more predominant in the ascending colon (.64/148) than in the descending colon (13/148). Examination of the apparently normal colon after the 20th injection of DMH revealed that both the ascending (P<O. 01) and descending colon epithelia (P< 0. 25) had a higher lebeling index than that of the control epithelia. Twelve rats which were given a single injection of DMH at a dose of 60 mg/kg of body weight were examined to observe the acute changes in the colon mucosa. This treatment induced a greater injurious effect on the ascending colon than on the descending colon with regard to crypt height and 3H-thymidine labeling index in the nucleus. Recovery from the damage was slower in the ascending colon than in the descenting colon. High iron diamine-Alcian blue staining of the colon epithelia disclosed that sulphomucin was decreased, while sialomucin was increased in the recovery stage m both the ascending and descending colon. These data indicate that the susceptibility of the colon to the carcinogenic effect of DMH differs by site and that the degree of cellular damage and repair by a single iniection of DMH reflects the cell kinetics following a prolonged DMH treatment and ultimate tumor yield. 51