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Mutagenic and Recombinogenic Effects of the Antitumor Antibiotic Anthramycin¹

College of Pharmacy [M. A. H., L. H. H.] and the Tobacco and Health Research Institute [C. G.], University of Kentucky, Lexington, Kentucky 40506

Anthramycin, one of the pyrrolo(1,4)benzodiazepine antibiotics with potent antitumor activity, was tested for its effects on a number of genetic parameters. The results show that this antibiotic is nonmutagenic in the Ames strains of Salmonella typhimurium while mutagenic in only one and antimutagenic in the rest of the genes tested in the eukaryotic organism Saccharomyces cerevisiae. The antibiotic is, however, a potent recombinogen inasmuch as it induced mitotic crossing over, mitotic gene conversion, and possibly other chromosomal alterations in a diploid strain of S. cerevisiae. These studies emphasize the need for a battery of test systems including eukaryotic organisms to detect the genetic activity of certain antitumor drugs. The importance of considering data distingui shing between highly mutagenic and poorly mutagenic cancer chemotherapeutic agents is also discussed.

¹ This work was supported by National Cancer Institute Grant CA-17047.

² To whom requests for reprints should be addressed.

Received 1/30/78. Accepted 6/ 6/78.