Mitomycin C is selectively toxic to proliferating cells in intact mammals, an effect presumably mediated by an inhibition of deoxyribonucleic acid synthesis. Actinomycin D is similarly cytotoxic but by a different mode of action. Both agents inhibit in vivo the incorporation of labeled thymidine into the DNA of rat small intestine, thymus, and bone marrow. Mitomycin causes prompt inhibition of thymidine incorporation and, simultaneously, of mitosis. These effects are seen in intestine within 1 hour after mitomycin injection, and they precede karyorrhexis and inhibition of RNA synthesis. Intestinal DNA, which has been prelabeled with thymidine-C14, is, however, stable for at least 2 hours after mitomycin treatment, though subsequently there are substantial losses of the label. In contrast to mitomycin's prompt action, the actinomycin effect on thymidine incorporation and on mitosis is characterized by a relatively long period of latency. Moreover, the actinomycin effect occurs together with or is preceded by karyorrhexis. Actinomycin also inhibits the incorporation of formate into RNA and DNA; these inhibitions appear simultaneously.
Aided by CCNSC Contract No. SA-43-p4-2445 from the National Cancer Institute, U.S.P.H.S.