This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Schwartz, H. S. Articles by Ambaye, R. Y. Search for Related Content PubMed PubMed Citation Articles by Schwartz, H. S. Articles by Ambaye, R. Y.

Actinomycin D: Drug Concentrations and Actions in Mouse Tissues and Tumors¹

Division of Pharmacology, Sloan-Kettering Institute for Cancer Research, New York, New York 10021

Concentrations of actinomycin D-³H in tissues and organs of mice were measured at 30 min and other times up to 48 hr after injection (600 µg/kg). Although this dose is sublethal for mice, it is known to damage cells of the intestinal epithelium, spleen, thymus, and the sensitive Ridgway osteogenic sarcoma (ROS). It has little or no cytotoxic effects on mouse liver or the solid, transplantable 7,12-dimethylbenz()anthracene (DMBA)-induced tumor. By 30 min, the average concentrations of labeled antibiotic in liver, salivary gland, and spleen (1.5–1.7 µg/gm) were already considerably higher than blood concentrations (0.1 µg/ml). Concentrations in other tissues were less: small intestine (0.8 µg/gm), ROS tumor (0.4 µg/gm), and DMBA tumor and thymus (0.2 µg/gm). Thereafter, concentrations decreased in liver, salivary gland, small intestine, and DMBA tumor while ROS and thymus continued to cumulate the antibiotic. By 48 hr, high concentrations were localized in spleen, thymus, and ROS, all of which are considered to be highly sensitive to the agent. Shorter retention times may be associated with moderate damage in salivary gland and small intestine and with little or no damage in liver and DMBA tumors. Uridine-³H incorporation into RNA was estimated at 3 hr after actinomycin, when most tissues had maximal drug concentrations, and at 24 hr, when most were depleted of drug. The inhibitory effects of actinomycin on incorporation rates were correlated with tissue levels of the drug but not with the susceptibility of the tissue to cytotoxicity.

¹ Aided by Grant CA 08748 from the National Cancer Institute, USPHS.

² Present address: Department of Biology, University of Alabama, University, Alabama 35486.

³ Visiting Fulbright-Hays Scholar.

Received 6/ 6/67. Accepted 10/ 3/67.