Isolation of Chinese hamster ovary cell mutants deficient in excision repair and mitomycin C bioactivation

Abstract

Mitomycin C (MMC), a bifunctional alkylating agent, requires metabolic reduction to become biologically active. We have identified a series of genetically related Chinese hamster ovary cell lines which span approximately three orders of magnitude in the concentration of MMC required for cell killing. Many mechanisms, including drug transport, drug activation, drug detoxification, and the elimination, or repair, of drug-induced lesions, may contribute to the level of drug resistance in cells. By exploring each of the above mechanisms in the various Chinese hamster ovary cell lines, we have been able to classify these cell lines into four categories. Proceeding from least resistant to most resistant to MMC, the cell lines are: (a) proficient in the bioreduction of MMC and deficient in DNA excision repair; (b) deficient in some aspects of MMC bioreduction and deficient in repair; (c) bioreduction and repair proficient; and (d) bioreduction deficient and repair proficient.