The effect of actinomycin D on radiation induced reactions of the lip mucosa of mice.
The interaction of intraperitoneally injected Actinomycin D and irradiation was investigated in the lip mucosa of NMRI mice. In this rapidly proliferating tissue, a semiquantitative assessment of possible modifications of the radiation response by a drug can be done without using lethality as an endpoint. It was shown that a single dose of 0.5 mg/kg drug given at different times between 24 hr prior to and 24 hr after single radiation doses did not effect the rate of development nor the intensity of mucosal radiation damage. With extended time intervals of 2, 3, or 7 days between both single agents, a slight increase of the lip mucosal reaction was measured. Similar results were obtained when 5 daily drug injections of 0.15 mg/kg were administered starting at day 5 after a single radiation exposure. No differences in response could be demonstrated when fractionated irradiations with intervals ranging from 1 to 24 hr were closely combined with either single or repeated drug treatments (0.5 mg/kg in total) as compared to irradiation alone. However, a slight modification of the iso-effect dose was measured when 0.5 mg/kg Actinomycin D was administered at various periods in between 2 radiation doses separated by 10 days. A maximal effect was measured with 5 daily injections of 0.15 mg/kg drug each and given at a time when proliferative capacity was high. With 0.1 mg/kg Actinomycin D per daily injection, no enhancement of the radiation injury was found. Thus, in these circumstances no influence of Actinomycin D on radiosensitivity nor on repair of sublethal damage could be demonstrated. A clear inhibitory effect on lip mucosal repopulation by the drug is evident, but only at high drug doses close to toxic concentrations.