Glutathione peroxidase protects cultured mammalian cells from the toxicity of adriamycin and paraquat.
Dihydrofolate reductase-minus mutants of Chinese hamster ovary cells were depleted of glutathione peroxidase by transcription of the transfected bovine cDNA in inverted orientation upstream from the cDNA for dihydrofolate reductase to engender a bicistronic mRNA. In a clone of cells selected for expression of dihydrofolate reductase by the ability to grow in nucleoside-free medium the activity of glutathione peroxidase was reduced to 20% of the activity in the untransfected parental line of cells (DG44). The cells depleted of glutathione peroxidase were more sensitive to the toxicities of paraquat and adriamycin than the untransfected parental cells from which they derived but not more sensitive to bleomycin, menadione, or phenazine methosulfate. That the mildly increased sensitivity to paraquat and adriamycin was the consequence of the diminished cellular content of glutathione peroxidase was confirmed by the increase in sensitivity of untransfected cells after treatment with buthionine sulfoximine, an agent which depletes cells of glutathione. These and other data strongly suggest that the enzymic action of glutathione peroxidase protects cells from the toxicity of paraquat and adriamycin. The toxin which these agents engender is likely to be hydrogen peroxide or another hydroperoxide upon which glutathione peroxidase acts.
Taylor
S D
SD
Department of Pathology, University of Utah School of Medicine, Salt Lake City.
Davenport
L D
LD
Speranza
M J
MJ
Mullenbach
G T
GT
Lynch
R E
RE
D000818:Animals; D019328:Buthionine Sulfoximine; D002374:Catalase / Q000378:metabolism; D002478:Cells, Cultured; D004317:Doxorubicin / Q000633:toxicity*; D005979:Glutathione Peroxidase / Q000378:metabolism*; D066298:In Vitro Techniques; D008322:Mammals; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives / Q000494:pharmacology; D010269:Paraquat / Q000633:toxicity*; D013482:Superoxide Dismutase / Q000378:metabolism; D014162:Transfection
D008717:Methionine Sulfoximine; D019328:Buthionine Sulfoximine; D004317:Doxorubicin; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D010269:Paraquat