Actinomycin D and Radiation Fractionation Studies in Asynchronous and Synchronized Chinese Hamster Cells

Using Chinese hamster cells grown, treated, and assayed in culture, we have examined the fractionation response relative to cell killing of two 30 minute exposures of actinomycin D, or a single exposure to this drug followed by a dose of x-rays. Asynchronous cells and cells synchronized by hydroxyurea treatment were used. We found that while an increase in 2-dose survival in 2 hours is observed with two actinomycin D exposures, this was very likely not due to repair of sublethal damage. It appeared, rather, that cell progression in the growth cycle to more resistant ages was probably responsible for the fractionation survival increase. Fractionation experiments in which a first dose of actinomycin D was followed at varying intervals by an x-ray dose supported this interpretation since we found that the drug damage able to interact with radiation damage persisted in time. In contrast to the situation when radiation is administered first, the DNA binding ability of actinomycin D probably accounts for the persistence of drug damage and the lack of significant sublethal damage repair during periods long enough for appreciable x-ray damage repair.