Increased catalase activity in mouse cell mutants resistant to paraquat

Paraquat is widely used as a generator of superoxide radicals in a cell. First it was shown to immediately induce premature senescence in normal human fibroblasts. To assess its defense mechanisms, we characterized three paraquat-resistant mutants from mouse FM3A cells, MPQR40-1 and MPQR40-3 isolated by a single-step selection after mutagenesis, and SPQR100-6 isolated spontaneously. All exhibited six to eight times more resistance to paraquat than the parental line. In cell-cell hybrids, their phenotypes were recessive, co-dominant, or dominant, respectively. Biochemical characterization revealed that activity and mRNA level for catalase were increased in all of the mutants. In MPQR40-3 that showed the highest degree of paraquat resistance, total SOD activity and mRNA level for Cu/Zn-SOD were also increased. These results suggest that catalase plays a major role in paraquat resistance in mouse FM3A cells.