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Role of Hypoxia in Anticancer Drug-induced Cytotoxicity for Ehrlich Ascites Cells¹

Division of Hematology-Oncology, Department of Internal Medicine, The University of Texas Medical Branch, Galveston, Texas 77550

A review of the literature on the effect of hypoxia on in vitro drug sensitivity had suggested that there was consistently more cytotoxicity under hypoxic conditions for the drugs misonidazole and mitomycin C while there was much conflicting data for the drugs Adriamycin and bleomycin. We have examined the effect of oxygen on the cellular response of Ehrlich's ascites tumor cells to the drugs mitomycin C, misonidazole, Adriamycin, and bleomycin. Significant differences were observed when we compared the cytotoxicity of mitomycin C and misonidazole as a function of oxygen concentration. For the drugs Adriamycin and bleomycin no differential effects of oxygen were noted for a 1-h drug exposure with hypoxia while some differences were noted only for bleomycin for an 8-h drug exposure time. Because differences dependent on oxygen concentration were observed for some drugs but not others at the same experimental conditions, and as indicated by a review of the literature, it is suggested that some of the conflicting data in the literature with respect to some of these drugs may be cell-line dependent. Other variables which may also be of importance were the duration of drug exposure time in hypoxia and cell density. The observed oxygen concentration-dependent changes in cell survival for the Ehrlich cells with drugs examined could not be explained on the basis of changes in drug-induced cellular oxygen consumption.

¹ Supported in part by USPHS Grant CA-32938, National Cancer Institute (NCI), and Cancer Center Grant CA-17701, NCI.

² To whom requests for reprints should be addressed, at Division of Hematology, Oncology/Internal Medicine Department, Clay Hall, H82, University of Texas Medical Branch, Galveston, TX 77550.

Received 4/ 9/86. Revised 12/ 2/86. Accepted 2/ 4/87.

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