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Resistance to Etoposide Induced by Three Glucose-regulated Stresses in Chinese Hamster Ovary Cells¹

Division of Radiation Biology, Roswell Park Memorial Institute, Buffalo, New York 14263

The induction of glucose-regulated proteins by a variety of specific inducers leads to an increase in resistance to Adriamycin (Shen et al., Proc. Natl. Acad. Sci. USA, 84: 3278, 1987). In this study we examine several additional agents for cross-resistance induced during a glucose-regulated response in an attempt to better define the mechanism through which this phenomenon occurs. When anoxia, calcium ionophore A23187, or 2-deoxyglucose are used, a substantial resistance is obtained against the topoisomerase II-targeted agent, etoposide. Partial resistance is induced against vincristine and actinomycin D. Glucose-regulated protein inducers do not substantially alter cellular response to either bleomycin or radiation. In the case of mitomycin C there is a cellular sensitization with anoxia and 2-deoxyglucose while calcium ionophore A23187 had no effect on survival. This study suggests that the resistance obtained during a glucose-regulated response against etoposide and Adriamycin may involve topoisomerase II.

¹ This work was supported in part by USPHS Grant 40330.

² Current Address: Department of Therapeutic Radiology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510. To whom requests for reprints should be addressed.

Received 7/25/88. Revised 2/20/89. Accepted 5/12/89.

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