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.