The Effect of Route of Administration and Radiation on ³H-Actinomycin D Binding by Mouse Hepatocyte DNA

The ability of hepatocyte nuclei from irradiated mice to bind ³H-actinomycin D was investigated at various times after exposure. Shortly after irradiation (1-3 hr), there was a marked drop in the amount of actinomycin bound by liver nuclei of ip-injected mice. The decreased binding after ip injection was probably an indirect action of radiation since it had no effect on binding iv-administered material. The decrease in actinomycin movement from the peritoneal cavity of similarly treated animals supports the hypothesis of an indirect action of radiation on binding by liver nuclei of ip-injected ³H-actinomycin D. Further evidence for the hypothesis derives from the in vitro experiments using nuclei irradiated either in vivo or in vitro, in which there was no influence of exposure on binding. When iv administration is used, the amount of actinomycin bound to nuclei is three times that when the drug is given ip. These data call attention to the importance of the route used to administer compounds when intrepreting either the action of the compound or those of radiation in animals.