Selective inhibition of replicative and repair DNA synthesis in mouse colon following administration of 1,2-dimethylhydrazine.

Abstract

Early alterations in normal semiconservative and repair DNA synthesis were determined in gastrointestinal tissues of HalCR mice following administration of the colon carcinogen 1,2-dimethylhydrazine (DMH). Following DMH injections of 60 and 200 mg/kg, normal DNA synthesis was rapidly inhibited in all tissues. The greatest depressions were observed in the descending colon, followed closely by the ascending colon. DNA repair was estimated by measuring unscheduled DNA synthesis. No repair was observable in the descending or ascending colon. The esophagus, forestomach, jejunum, and ileum demonstrated significant amounts of DNA repair, while the duodenum and gastric stomach displayed nominal or insignificant amounts of repair. Repair DNA synthesis was inhibited by simultaneous administration of caffeine and DMH. The degree of inhibition of normal replicative DNA synthesis and the amount of repair DNA synthesis in response to DMH treatment correlate closely with the incidence of DMH-induced tumors. Most tumors occur in the descending colon, followed by the ascending colon, and only a few in the duodenum and gastric stomach area. Neoplasms are rarely found in the remainder of the gastrointestinal system.