Hypoxia-induced drug resistance: comparison to P-glycoprotein-associated drug resistance.
In this report, we investigate several examples of hypoxia-induced drug resistance and compare them with P-glycoprotein associated multidrug resistance (MDR). EMT6/Ro cells exposed to drugs in air immediately after hypoxic treatment developed resistance to adriamycin, 5-fluorouracil, and actinomycin D. However, these cells did not develop resistance to colchicine, vincristine or cisplatin. When the cells were returned to a normal oxygen environment, they lost resistance. There was no correlation between the content of adriamycin and the development of adriamycin resistance induced by hypoxia. There was no difference between the efflux of adriamycin from aerobic cells and that from hypoxia-treated cells. The mRNA for P-glycoprotein was not detected in the hypoxia-treated cells. These results suggest that hypoxia-induced drug resistance is different from P-glycoprotein associated multidrug resistance.
Laboratory of Cell and Molecular Biology, Life Sciences Division SRI International, Menlo Park, California 94025.
K
K
Sakata
T T
TT
Kwok
B J
BJ
Murphy
K R
KR
Laderoute
G R
GR
Gordon
R M
RM
Sutherland
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D015152:Blotting, Northern; D016466:CHO Cells; D002453:Cell Cycle / Q000502:physiology; D015687:Cell Hypoxia / Q000502:physiology*; D006224:Cricetinae; D004247:DNA / Q000032:analysis; D003609:Dactinomycin / Q000494:pharmacology; D004317:Doxorubicin / Q000493:pharmacokinetics / Q000494:pharmacology; D004351:Drug Resistance / Q000502:physiology*; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D008562:Membrane Glycoproteins / Q000378:metabolism* / Q000502:physiology; D014407:Tumor Cells, Cultured / Q000378:metabolism
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D008562:Membrane Glycoproteins; D003609:Dactinomycin; D004317:Doxorubicin; D004247:DNA; D005472:Fluorouracil