Resistance to etoposide induced by three glucose-regulated stresses in Chinese hamster ovary cells.
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.
Hughes
C S
CS
Division of Radiation Biology, Roswell Park Memorial Institute, Buffalo, New York 14263.
Shen
J W
JW
Subjeck
J R
JR
D000818:Animals; D000001:Calcimycin / Q000172:deficiency; D006224:Cricetinae; D003412:Cricetulus; D003609:Dactinomycin / Q000378:metabolism; D003847:Deoxyglucose / Q000172:deficiency; D004317:Doxorubicin / Q000378:metabolism; D004351:Drug Resistance; D005047:Etoposide / Q000378:metabolism*; D005260:Female; D018840:HSP70 Heat-Shock Proteins; D000860:Hypoxia / Q000378:metabolism; D008565:Membrane Proteins / Q000096:biosynthesis*; D010051:Ovarian Neoplasms / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000378:metabolism; D014750:Vincristine / Q000378:metabolism
D018840:HSP70 Heat-Shock Proteins; D008565:Membrane Proteins; C018551:glucose-regulated proteins; D003609:Dactinomycin; D000001:Calcimycin; D014750:Vincristine; D005047:Etoposide; D004317:Doxorubicin; D003847:Deoxyglucose