Abstract
This study was undertaken to elucidate the mechanism of cross-resistance to mitomycin C (MMC) in a multi-drug resistant mouse leukemia cell line ( P388 R-84 ). The P388 R-84 cells were 6.2-fold more resistant to MMC as compared to the sensitive cells ( P388 S ). Since oxygen radical formation has been suggested to be important in MMC cytotoxicity, MMC-dependent peroxidation of membrane lipids (an index of oxygen radical formation) was compared in these cell lines. MMC-dependent lipid peroxidation was 2.56-fold higher using P388 S cell extract when compared to that of P388 R-84 cells. Depletion of cellular glutathione (GSH) levels in the resistant cells produced a 1.76-fold increase in MMC-dependent lipid peroxidation. MMC cytotoxicity was also increased significantly by GSH depletion in P388 R-84 cells. These results suggest that cellular resistance to MMC in P388 R-84 cells may, at least in part, be due to the reduced formation of oxyradicals in these cells.
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