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Effects of Actinomycin D on Cell Cycle Kinetics and the DNA of Chinese Hamster and Mouse Mammary Tumor Cells Cultivated in Vitro¹

Department of Radiology, Stanford University School of Medicine, Stanford, California 94305

Actinomycin D produces changes in the cell cycle kinetics of Chinese hamster (HA1) and mouse mammary tumor cells (EMT6) cultivated in vitro. There was a reduced rate of progression of the cells through S phase and a G₂ arrest, the duration and degree of which were drug dose dependent. The lethal effects of the drug on the two cell lines were comparable.

At the molecular level, DNA single-strand breaks (true breaks and/or alkali-labile bonds) appear initially. After drug removal, the extent of disappearance of these DNA strand breaks was drug dose dependent. Similar results were obtained for the two cell lines. However, at the lower drug concentration (0.1 µg/ml), although the DNA strand breaks appeared to disappear after drug free incubation, about 60% of this cell population was not viable.

¹ This work was supported by Research Grant ET-3 from the American Cancer Society and Program Project Grant CA-10372 from the National Cancer Institute, Department of Health, Education and Welfare.

Received 3/24/76. Accepted 6/18/76.