Relationship of colonic mucosal background to neoplastic proliferative activity in dimethylhydrazine-treated mice

Proliferative activity of background and neoplastic colonic mucosa was examined following five months of weekly injections of 1,2-dimethylhydrazine (20 mg/kg) and one or four months of rest to determine whether previously reported changes may result from an acute or chronic effect of dimethylhydrazine and whether differences exist between stages of neoplasia. To determine whether neoplasia is responsive to a proliferative stimulus, 1,2-dimethylhydrazine dihydrochloride-treated mice were inoculated with Citrobacter freundii. The labeling index and the proliferative zone increased in background mucosa after one month; whereas after four months labeling index, proliferative zone and crypt heights increased, but the mitotic index decreased. There was a positive linear correlation between advancing tumor grade and increasing tumor labeling index and mitotic index. Background labeling index, even when elevated by C. freundii inoculation, had no effect upon tumor labeling index. Mitotic index diminished in background and neoplastic mucosa following prolonged rest and increased in both following C. freundii inoculation. These studies show that 1,2-dimethylhydrazine dihydrochloride causes long-term changes in background mucosa that are apart from a reparative response to cytotoxicity. As tumors progress, labeling index and mitotic index increase, suggesting a multistage process of evolution.