Changes in crypt cell populations of mouse colon during recovery from treatment with 1,2-dimethylhydrazine

The induction of adenocarcinomas in distal colons of noninbred female Swiss Webster white mice by 1,2-dimethylhydrazine (DMH) is preceded by the development of hyperplasia of mucosal glands, which includes absolute increases in both the total number of cells and labeled cells per crypt. This experiment was designed to determine if these changes are reversible. Groups of noninbred female Swiss Webster white mice were given weekly injections of DMH, 20 mg/kg body weight, for 1--20 weeks and killed 1--52 weeks after treatment. Animals were pulsed with tritiated thymidine ([3H]dTHd) for 1 hour and autoradiographs were made of sections of distal colon. The total number of cells per crypt and number of [3H]dThd-labeled cells per crypt were significantly elevated in animals killed 1 week after termination of treatment. With increasingly longer periods of recovery, base-line values were reached rapidly in animals given one or two treatments; however, reduction in cells was slower and less complete in animals given eight or more treatments. The latency before tumors developed was inversely related to the number of treatments. Animals that received 20 treatments developed more tumors per tumor-bearing animal than did animals given fewer treatments but allowed by survive for long periods. The findings indicate that once induced changes in the mucosa progress to a threshold level, mucosal glands are irreversibly enlarged and the development of tumors is irrevocable.