Single, lethal doses of actinomycin D (1 mg/kg) promptly decreased the rate of incorporation of C14-orotate into nuclear ribonucleic acid of liver in intact and hepatectomized rats. The inhibition was transient, despite morphologic changes that appeared at 3 hr., and was fully reversed by 16 hr. in intact liver and partially so in regenerating liver. In regenerating liver, mitotic inhibition was also seen at 1 hr. and became maximal by 16 hr. Thymidine incorporation into deoxyribonucleic acid (DNA) of regenerating liver, though only slightly affected during the first hour, diminished markedly by 16 hr. Tryptophan pyrrolase activity, assayed in homogenates of intact liver, was stimulated in control animals for at least 4 hr. after ether anesthesia and I.V. saline injections; it returned to basal levels at 16 hr. Actinomycin prevented the initial stimulation. Leucine incorporation in protein was not inhibited directly in intact liver; in regenerating liver moderate inhibitions developed slowly. Higher doses of actinomycin (5 mg/kg) inhibited thymidine incorporation in DNA (80% by 1 hr.) and leucine incorporation in protein (30–40% by 4 hr.).
This study was aided by Cancer Chemotherapy National Service Center contract SA-43-ph-2445 and grant CA-03192 from the National Cancer Institute, USPHS. A preliminary report was presented in Proc. Am. Assoc. Cancer Research, 5: 57, 1964.