Resistance to etoposide induced by three glucose-regulated stresses in Chinese hamster ovary cells.

ABSTRACT

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.