Early effects of sublethal doses have been compared in sensitive Ridgway osteogenic sarcoma (ROS) and resistant (DMBA) tumors [designation for a spindle cell sarcoma originally induced in AKR mice with 7,12-dimethylbenz(α)anthracene] and in small intestine in mice. Doses of actinomycin which were tumoricidal for the sensitive tumor were also toxic to intestinal crypt cells; DNA synthesis, estimated with pulses of labeled precursors, was almost completely blocked in 24 hr in ROS and intestine, while RNA synthesis was unaffected or only partially inhibited. At earlier times (2, 4, and 8 hr) RNA synthesis was also inhibited partially while DNA synthesis was unaffected. These results show that extreme inhibition of precursor incorporation into RNA by actinomycin in susceptible cells is not a necessary antecedent to cytotoxicity in vivo. RNA, DNA, and protein concentrations were measured in ROS and DMBA tumors and in intestine. The only significant change occurred in ROS which lost 30–40% of its RNA within 24 hours after treatment. Since the ROS tumor is more susceptible to damage than are other tissues, the extensive loss of RNA may be associated with actinomycin's tumoricidal action.
Aided by Grant CA 08748 from the National Cancer Institute, USPHS.