Cross-resistance studies on two K562 sublines resistant to diaziridinylbenzoquinones.
Two resistant K562 sublines have been developed by treatment with AZQ (2,5-bis(carboethoxyamino)-3,6-diaziridinyl-1,4-benzoquinone) and BZQ (2,5-bis(2-hydroxyethylamino)-3,6-diaziridinyl-1,4-benzoquinone). The ID50 values of for AZQ on K562, the AZQ-resistant sublines (AZQR) and the BZQ-resistant sublines (BZQR) were 0.063, 1.47 and 0.244 microM, respectively. The relative ID50 values for BZQ on the same cell lines were 0.2, 0.67 and 0.83 microM, respectively. Although it is generally believed that these two quinones function by different mechanisms, the two sublines have similar decreased levels of cytochrome P-450 reductase and DT-diaphorase and increased levels of glutathione and superoxide dismutase, compared to the parent cell line. The sublines are also cross-resistant to adriamycin, mitozolamide, N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and mitomycin C. This work indicates the potential multifactorial mechanisms by which drug resistance can be induced in cell lines in the absence of conventional 'P'-glycoprotein multidrug resistance.
Ward
T H
TH
CRC Department of Cell Culture, Paterson Institute for Cancer Research, Christie Hospital, Manchester, U.K.
Haran
M S
MS
Whittaker
D
D
Watson
A J
AJ
Howard
T D
TD
Butler
J
J
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000032:analysis; D001388:Aziridines / Q000494:pharmacology*; D016227:Benzoquinones / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D005978:Glutathione / Q000032:analysis; D006801:Humans; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000032:analysis; D009251:NADPH-Ferrihemoprotein Reductase; D010088:Oxidoreductases / Q000032:analysis; D013482:Superoxide Dismutase / Q000032:analysis
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D001388:Aziridines; D016227:Benzoquinones; C045315:NSC 224070; D010088:Oxidoreductases; D013482:Superoxide Dismutase; D009251:NADPH-Ferrihemoprotein Reductase; D016660:NAD(P)H Dehydrogenase (Quinone); C029108:diaziquone; D005978:Glutathione