Vincristine resistant HL-60 cells show cross-resistance to hypoxanthine-xanthine oxidase.
This is the first observation that active an oxygen-producing system showed cross-resistance to vincristine (VCR) resistant cells or other anticancer agent-resistant cells. The extent of cross-resistance against oxygen radicals and anticancer agents in wild type and VCR resistant human promyelocytic leukemia cell line, HL-60 and HL-60/VCR, is compared. Superoxide was generated by reaction with hypoxanthine(HX)-xanthine oxidase(XO). HL-60/VCR was 81-fold resistant to VCR, 11.8-fold resistant to adriamycin, and 8.5-fold resistant to the XO concentration required for 50% growth inhibition compared with HL-60. Because oxygen radicals injure the cell membrane, the results indicate an increased resistance to membrane damage by oxygen radicals in drug resistant cells.
Hirose
M
M
Division of Transfusion Medicine, Tokushima University School of Medicine, Japan.
Fukuzawa
K
K
Kuroda
Y
Y
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D018922:HL-60 Cells / Q000187:drug effects*; D006801:Humans; D019271:Hypoxanthine; D007042:Hypoxanthines / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism / Q000633:toxicity*; D014527:Uric Acid / Q000378:metabolism; D014750:Vincristine / Q000494:pharmacology*; D014969:Xanthine Oxidase / Q000378:metabolism*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D007042:Hypoxanthines; D017382:Reactive Oxygen Species; D014527:Uric Acid; D019271:Hypoxanthine; D014750:Vincristine; D014969:Xanthine Oxidase