Joint lethal effects of actinomycin D and radiation in mice.

These studies are primarily concerned with recovery from sublethal actinomycin D or radiation damage as measured by joint lethality of the two treatments separated by an interval of 1 hr to 4 days. In mice given actinomycin D and challenged with radiation, the high mortality attributable to joint treatment decreased steadily between the 6-hr and the 3-day challenge. On the other hand, in mice given radiation and challenged with actinomycin D 6 to 24 hr later, there was no evidence of recovery from the radiation damage, survival remaining at or below the 20% level seen when actinomycin D and radiation were given together. This is unlike the result obtained with a divided radiation dose, where survival was markedly increased when the second fraction was given 3 to 6 hr or 24 hr after the first. Thus, there exists a residual effect of radiation not uncovered by a second irradiation, but clearly demonstrated when the challenge is an injection of actinomycin D. Estimated parameters of the 28-day dose-survival curves for actinomycin D alone and radiation alone were essentially the same when a factor for rads/Mg actinomycin D was supplied. When actinomycin D was given 1 hr before irradiation, dosewise additivity at the 50% response level was approximately 85%. Application of this factor gives dose-response curves for joint treatment with the same characteristics as those observed for mice given either treatment alone. For equal 28-day mortality, however, there was a significantly higher percentage of deaths 6 to 9 days after treatment in the mice given actinomycin D than in mice given radiation alone.