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Ultrarapid Recovery from Lethal Effects of Bleomycin and -Radiation in Stationary-Phase Human Diploid Fibroblasts¹

Department of Radiation Biology and Biophysics, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642 [C. W. M.]; Harvard University, Laboratory of Radiobiology, School of Public Health, Boston, Massachusetts 02115 [C. W. M., A. W. M., K. N. T., J. B. L.]; and Joint Center for Radiation Therapy, Harvard Medical School, Boston, Massachusetts 02115 [A. W. M., K. N. T.]

An ultrarapid phase of cellular recovery, as measured in liquid holding type experiments, was studied in stationary-phase human fibroblasts exposed to bleomycin or cobalt-60 -irradiation yielding comparable levels of cell killing. This rapid recovery was both faster and considerably greater in magnitude after bleomycin treatments. Bleomycin survival curves were multiphasic, indicating the presence of treated cells with varying sensitivities either at the beginning of treatments or as a result of resistance which developed during the treatment period. The amount of both ultrarapid (within 2 to 10 min) and slower recovery was dose dependent after irradiation with 200 to 800 rads or 30-min exposures to bleomycin (5 to 100 µg/ml). Following belomycin treatments resulting in surviving fractions of 1 to 2%, survival increased up to 8-fold after only 2 min of posttreatment incubation. This rapid increase in survival was followed by a slower increase over time periods up to 3 h. In contrast, the rates of cellular recovery after -irradiation were more gradual from 0 to 3 h. Recovery at all posttreatment intervals was always greater after bleomycin than after -treatments, following doses yielding 1 to 50% survival. The ultrarapid component of cellular recovery after bleomycin treatments may have implications for both clinical cancer management and cellular studies directed toward determining mechanisms of action of belomycin.

¹ This paper has been numbered University of Rochester Report UR-3490-2036.

² Supported by USPHS Grant CA25609 awarded by the National Cancer Institute and by grants from the United Cancer Council, Inc. (Rochester), Rockefeller Foundation to the Harvard Interdisciplinary Programs in Health program, and American Cancer Society, Inc. (IN18; New York, NY). To whom requests for reprints should be addressed.

³ Supported by USPHS Grant CA11751 awarded by the National Cancer Institute.

Received 12/14/81. Revised 8/27/84. Revised 12/11/84. Accepted 1/10/85.

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