Paraquat-resistant HeLa cells: increased cellular content of glutathione peroxidase

Paraquat-resistant HeLa cells were selected and characterized to determine the mechanism(s) of the toxic action of paraquat for cultured mammalian cells. From HeLa cells already selected for resistance to the toxicity of 40 microM paraquat more resistant cells were selected in 90 microM paraquat. In these more resistant cells (PQRHM90) one adaptation which occurred at the lesser concentration of paraquat, magnification of the cellular content of both the CuZn- and the Mn-containing superoxide dismutases, did not increase further. Instead, the cellular content of catalase and of glutathione peroxidase increased. The increased cellular content of glutathione peroxidase appeared more likely to have produced increased resistance to paraquat than did the augmented content of catalase because, after cultivation in the absence of paraquat, the cells retained both resistance to 90 microM paraquat and the increased content of glutathione peroxidase, while the content of catalase declined. The cellular content of reduced glutathione in the PQRHM90 cells grown in paraquat was diminished in comparison with that in the cells from which they derived. The data suggest that the PQRHM90 cells resisted the toxicity of paraquat by increasing the cellular activity of glutathione peroxidase as a means of detoxifying the H2O2 produced by paraquat.