Development and initial characterization of a mitomycin C-resistant colon cancer cell line variant

Resistance may limit the clinical usefulness of a variety of chemotherapeutic drugs, including mitomycin C (MMC). In order to study resistance to MMC, a variant of the HT-29 human colon cell line was isolated by exposure to repeated doses of MMC. The 95% inhibitory concentration of MMC for this isolate (HT-29R13) was found to be approximately twice that for the parent line. The level of resistance did not increase with additional drug exposure, and resistance was stable for at least 6 months in the absence of drug exposure. HT-29R13 cells exhibit cross-resistance to melphalan and 5-FU but not to doxorubicin, cis-platinum, or etoposide. HT-29R13 cells are characterized by slightly decreased plating efficiency and slightly increased total protein compared with the parent line. This model of stable, low-level MMC resistance with an unusual cross-resistance pattern may prove useful for the study and characterization of MMC resistance mechanisms.