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Enhancement of Toxicity from N-(2-Chloroethyl)-N'-cyclohexyl-N-nitrosourea in V79 Spheroids by a Nitrofuran¹

Medical Biophysics Unit, British Columbia Cancer Research Centre, Vancouver, British Columbia, Canada V5Z 1L3

Hypoxic cell radiosensitizers enhance the cytotoxicity of several common chemotherapeutic agents in vitro and in vivo. Although this process has generally been called sensitization, few studies have documented true potentiation. We have used Chinese hamster V79 spheroids to study chemosensitization and fluorescence-activated cell sorting to specifically evaluate the roles of sensitizer binding and hypoxia in the effect. By using the median effect analysis to quantify the interactions of the agents, we conclude that marked potentiation can indeed be achieved. Somewhat greater potentiation was observed at increased depths within the spheroids, but the relative change was less than predicted on the basis of the decreasing oxygen tension. Further, increased toxicity did not necessarily lead to increased chemopotentiation, nor was potentiation directly related to the metabolism/binding of the nitrofuran. Thus, chemopotentiation is clearly a complicated process, highly dependent upon the sensitizer to antitumor drug ratio and the exposure conditions.

¹ Supported by the National Cancer Institute of Canada and by NIH Grants CA-37879 and CA-37775.

² To whom requests for reprints should be addressed, at Medical Biophysics Unit, British Columbia Cancer Research Centre, 601 West 10th Avenue, Vancouver, B.C. V5Z 1L3, Canada.

Received 11/24/86. Revised 6/ 3/87. Accepted 7/14/87.