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Tumorigenicity in Vivo and Induction of Malignant Transformation and Mutagenesis in Cell Cultures by Adriamycin and Daunomycin¹

Laboratory of Pharmacology, Sloan-Kettering Institute for Cancer Research, and Department of Pathology, Memorial Hospital, New York, New York 10021

The two anthracycline antitumor antibiotics, adriamycin and daunomycin, have been tested for tumorigenic activity, and the results confirm previous findings that they can induce mammary tumors in female rats receiving single i.v. doses. Both substances are highly potent in producing malignant transformation and mutation in mammalian cell systems in vitro. Their transforming activity is comparable to that of the potent carcinogen, N-methyl-N'-nitro-N-nitro-soguanidine. Actinomycin D, although similar to the anthracyclines in having high binding affinity for DNA, is only minimally effective in the same in vitro systems and its direct carcinogenic activity in vivo is moot. These results suggest that satisfactory correlations may be obtainable between tests for tumorigenicity in vivo and assays for transformation and mutagenesis in vitro, and that adriamycin and daunomycin may have carcinogenic potential in man.

¹ Supported in part by Grants CA 08748 and CA 15205 from the National Cancer Institute, USPHS. Preliminary reports of some of these data have appeared (17, 21).

² Recipient of Research Career Development Award 1 KO 4 CA 00127, NIH, USPHS.

Received 11/20/75. Accepted 3/ 2/76.

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