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Temperature Effect on Mitoxantrone Cytotoxicity in Chinese Hamster Cells in Vitro

Methodist Hospital, Brooklyn 11215, and Downstate Medical Center, State University of New York, Brooklyn, New York 11203

The effect of heat on 1,4-dihydroxy-5,8-bis{2-[(2-hydroxyethyl)amino]ethylamino}-9,10-anthracenedione dihydrochloride (DHAD; mitoxantrone, NSC 301739) cytotoxicity was studied in V79 Chinese hamster cells. An overnight exposure to the drug at 40°C enhanced drug damage in chromosome aberrations, culture growth, and cellular reproductive integrity. Preincubation of cells overnight in medium containing no drug at this temperature also showed some enhancement in subsequent DHAD lethality (at 37°C as well as 43°C). Short exposures (1 h) to DHAD at 43°C was more damaging than were exposures at 37°C. This was also true for cells in the plateau phase of culture growth. As compared with exponentially growing cells, plateauphase cells were more resistant to DHAD.

¹ To whom requests for reprints should be addressed, at Department of Radiotherapy, Methodist Hospital, 506 Sixth Street, Brooklyn, NY 11215.

Received 5/14/84. Revised 4/30/85. Accepted 5/ 1/85.