Experimental studies with actinomycin D.

Actinomycin D has been tested on mouse tu mors, with varying degrees of success, as an anti-neoplastic agent. Dramatic inhibition of some ascites (mouse) tumors has been reported by Sugiura (14) and Gregory et al. (6). Reilly (11) and Sugiura (14) are in agreement that actino-mycin D has slight antineoplastic activity against S-180, and Farber (3) demonstrated antitumor activity against the malignant melanoma S-91, mammary adenocarcinoma, and both myeloid and lymphoid leukemia. Fantini et al. (2) confirmed the activity of actinomycin D and reported a glio-blastoma, S-91 melanoma, and a C3H mammary adenocarcinoma as being most sensitive to this antibiotic. No definitive discussion of the uses of actino mycin D for human therapy has been published, although French and German authors (4) have reported that patients in the early stages of Hodgkins disease and other lymphomas have benefited from actinomycin C. The negative effect of actinomycin D on Hodgkins disease was dis cussed by Korst and Meyer (8). Farber et al. (4) reported no effect against acute leukemia in chil dren, although temporary changes were observed in children with rhabdomyosarcoma, Wilm's tu mors, and Hodgkins disease. The investigation herein reported elucidates the activity of actinomycin D on animal tumors. It includes toxicity studies of pathological changes attributable to the material. Additionally, actino mycin D was studied on a variety of tumors to determine the types against which it has the most effective antitumor action. To ascertain the corre lation between in vitro anticell activity and in vivo antitumor activity, in vitro tests are described. In vitro tests were used to further evaluate this rapid technic for selecting chemicals for cancer chemo therapy. MATERIALS Solutions of actinomycin D were made by dis solving actinomycin in 1 part ethanol and 4 parts * This investigation was supported in part by a research grant from the Rosenstiel Foundation. water. From a solution of 100 fig/ml all other solutions were made by further dilution with saline. The tumors in the present study included solid Sarcoma 180 from Dr. D. Clarke, solid and ascites forms of Ehrlich and Krebs-2 carcinoma from Dr. T. S. Hauschka, all in Swiss albino mice. Mammary carcinoma C3HBA was propagated in C3H mice and adenocarcinoma C-755, obtained from Dr. A. Gellhorn, was grown in C57BL/6 mice. Also used was DBA/2 thymoma, obtained from Dr. T. S. Hauschka, grown subcutaneously in DBA/1 mice. A cocker spaniel with a spontaneous adenocarcinoma of …