Paraquat and radiation effects on mouse C3H 10T1/2 cells

The dipyridilium compound, paraquat, has been used in conjunction with mouse C3H 10T1/2 cells to determine if this superoxide (O2-) generating agent acts to oncogenically transform, chromosomally alter or influence cytokinetics or cellular survival. Paraquat alone is a cytotoxic agent and is additionally a weak radiosensitizer. A 0.1 mM 24 hour treatment results in about 30% cell survival and enhances the cell killing effects of 137Cs gamma rays by a factor of about 1.2. The drug appears to function lethally by initiating an interphase cell death, and additionally slows the movement of cycling cells through the cell cycle. It is a poor inducer of SCE's and combined effects with radiation are strictly additive. Paraquat oncogenically transforms cells but not in a dose-dependent manner, yet combined treatments with 3 Gy result in transformation frequencies greater than expected for additive effects. Depending on the endpoint examined, which may be related to the degree of nuclear involvement, paraquat either acts additively (SCE's) or with greater than an additive effect (cell survival and oncogenic transformation).