This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services 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 Philips, F. S. Search for Related Content PubMed PubMed Citation Articles by Schwartz, H. S. Articles by Philips, F. S.

Actinomycin D: Effects on Ridgway Osteogenic Sarcoma in Mice¹

Division of Experimental Chemotherapy, Sloan-Kettering Institute for Cancer Research, New York, New York

Destruction of Ridgway osteogenic sarcoma (ROS) tumor in AKR mice occurs after single i.v. injections of actinomycin D. Optimal doses for full regression of the tumor were 800–1200 µg/kg. Doses of 400 µg/kg were only partially effective and those of 1600 µg/kg were lethal. The therapeutic response probably occurs without assistance by host immune mechanisms. This was demonstrated by the successful growth of 2nd implants in animals in which primary tumors were regressing after treatment by the agent. When actinomycin was given by i.p. route, mice were lethally intoxicated by 1200 µg/kg, even though this dose was tolerated when administered by i.v. route. Tissues were taken from tumor-bearing mice for pathologic examination at various times after i.v. and i.p. administration of actinomycin D (800 µg). Recovery of nucleated elements in spleen of mice treated i.p. was markedly delayed by comparison with that found after i.v. doses. Other tissues (e.g., small intestine, thymus, and liver) as well as tumor were not differentially affected by the 2 routes. Twenty-four hr after treatment (800 µg/kg by either route), tumor tissue was no longer compact as in controls, and numerous fragmented nuclei were present. By 4 days necrosis was almost complete and, at 7 and 15 days, tumors were reduced to partially calcified, necrotic masses with multinucleate giant cells. These changes were confined to regressing tumors and were not seen during tumor growth.

¹ This research was supported by Grant CA-03192 from the National Cancer Institute, USPHS.

² Visiting Investigator, Chester Beatty Research Institute, London, September 1965 to July 1966, during tenure of an Alfred P. Sloan Award in Cancer Research.

Received 2/10/66.