Paraquat-Resistant HeLa Cells
The cytotoxic action of chemicals which transfer electrons from biological reductants to molecular oxygen is believed to result from the formation of •O2-, H2O2, and •OH. Paraquat is one such agent which appears to act in Escherichia coli primarily by generating •O2-, but necessarily H2O2 as well. To have its cytotoxic action by promoting the intracellular formation of •O2- paraquat must first be taken up by the cell, it must then be reduced by one electron to form the paraquat radical, and finally it must auto-oxidize to yield •O2-. If this scheme is correct for mammalian cells as it appears to be for prokaryotes,1 cells which adapt to growth in the presence of paraquat should modify one or more of these steps, probably by mutation or other genetic adaptation, such as amplification of genes for the superoxide dismutases or for catalase, as a means of increasing the cellular content of enzymes which scavenge •O2- or H2O2, respectively.
KeywordsSuperoxide Dismutase Dihydrofolate Reductase Cellular Content Biological Reductant CuZn Superoxide Dismutase
Unable to display preview. Download preview PDF.
- 2.R. A. Hallewell, F. R. Masiarz, R. C. Najarian, J. P. Puma, M. R. Quiroga, A. Randolph, R. Sanchez-Pescador, C. J. Scandella, B. Smith, K. S. Steimer, and G. T. Mullenbach, Human Cu/Zn superoxide dismutase cDNA: isolation of clones synthesizing high levels of active or inactive enzyme from an expression library, Nucleic Acids Res. 13:2017 (1985).PubMedCrossRefGoogle Scholar
- 4.C. Gorman, High efficiency gene transfer into mammalian cells, in: “DNA Cloning, Volume II,” D. M. Glover, ed., IRL Press, Oxford & Washington, D. C. (1985).Google Scholar