Chinese hamster ovary cells resistant to okadaic acid express a multidrug resistant phenotype.
Two Chinese hamster ovary cell clones resistant to okadaic acid (OA) were isolated. The OA-resistance was associated with resistance to colchicine, Vinca alkaloids and inhibitors of DNA topoisomerase (topo) II. Drug accumulation assays showed that the intracellular levels of OA, vinblastine and vincristine, but not the topo II inhibitor etoposide, were significantly lowered in the OA-resistant mutants than in the parental cells. These results, together with the finding of an increased level of P-glycoprotein (P-gp) in the mutant cells, indicate that the resistances to OA, Vinca alkaloids and colchicine are due to a P-gp-mediated mechanism. Resistance to topo II inhibitors, however, was associated with reduced activity of topo II. Thus, at least two events, overexpression of P-gp and reduction of topo II activity, occurred in a single OA-resistant cell line, contributing to expression of the MDR phenotype.
Tohda
H
H
Department of Neurochemistry and Molecular Biology, Tohoku University, Sendai, Japan.
Yasui
A
A
Yasumoto
T
T
Nakayasu
M
M
Shima
H
H
Nagao
M
M
Sugimura
T
T
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000818:Animals; D016466:CHO Cells / Q000187:drug effects*; D002352:Carrier Proteins / Q000378:metabolism; D003078:Colchicine / Q000378:metabolism; D006224:Cricetinae; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D004351:Drug Resistance; D004988:Ethers, Cyclic / Q000378:metabolism / Q000494:pharmacology*; D008562:Membrane Glycoproteins / Q000378:metabolism; D019319:Okadaic Acid; D010641:Phenotype; D059005:Topoisomerase II Inhibitors; D014747:Vinblastine / Q000378:metabolism; D014748:Vinca Alkaloids / Q000378:metabolism; D014750:Vincristine / Q000378:metabolism
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002352:Carrier Proteins; D004988:Ethers, Cyclic; D008562:Membrane Glycoproteins; D059005:Topoisomerase II Inhibitors; D014748:Vinca Alkaloids; D019319:Okadaic Acid; D014750:Vincristine; D014747:Vinblastine; D004250:DNA Topoisomerases, Type II; D003078:Colchicine