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Differential Effect of Adriamycin on DNA Replicative and Repair Synthesis in Cultured Neonatal Rat Cardiac Cells¹

Department of Biological Sciences, Molecular Biology Section, University of Southern California, University Park, Los Angeles, California 90007 [H. F., M. F. G.], and Center for Health Sciences, School of Nursing, University of California, Los Angeles, Los Angeles, California 90024 [M. W. S.]

The effect of the potent antitumor antiobiotic Adriamycin (ADM) on DNA replication and unscheduled DNA synthesis in cultured rat cardiac cells was investigated. Autoradiography and [³H]thymidine incorporation studies were carried out on parallel cultures. DNA replication was depressed for up to 6 days following a 3-hr pulse of ADM administration. An ADM concentration of 1 µg/ml which was effective in reducing replicative DNA synthesis by as much as 75% did not reduce the ability of cardiac cells to repair UV-damaged DNA. However, cells exposed to higher ADM concentrations failed to undergo significant UV-induced repair. In the absence of UV treatment, ADM did not stimulate unscheduled DNA synthesis. To account for the differential response of the cardiac cell cultures to replicate and repair DNA, we propose that ADM exerts a localized effect on DNA synthesis covering a region proximal to its primary intercalation site.

¹ Supported by NIH Grants CA17358 and GM21422 and grants from the University of California Cancer Research Coordinating Committee and American Heart Association, Greater Los Angeles affiliate.

² To whom requests for reprints should be addressed.

Received 5/15/78. Accepted 1/12/79.