Oxidative Damage: DNA Repair and Inducible Resistance
Free radicals and activated oxygen species are generated in a variety of ways. For example, most of the biological effects of ionizing radiations can be ascribed to the oxygen radicals they produce, such as superoxide anion (O2 \(\overline \bullet \)) and hydroxyl radical (·OH) (1). Such radicals are also produced deliberately by macrophages during inflammatory responses, evidently as a means of destroying invading cells (2). It seems likely that the normal reduction of O2 to water by cytochrome C oxidase might inadvertently release intracellular activated oxygen. Indeed, bacteria devoid of superoxide dismutase, which destroys O2 \(\overline \bullet \), display a strongly increased spontaneous mutation frequency in aerated but not in hypoxic culture (3). This apparent production of oxygen radicals under normal aerobic conditions underscores the need to understand the nature of the cellular defenses against oxidative damage. We are investigating the mechanisms that cells employ to avert oxidative damage and to correct such damage when it does occur.
KeywordsAtaxia Telangiectasia Cumene Hydroperoxide Hypoxic Culture Alkyl Hydroperoxide Reductase Spontaneous Mutation Frequency
Unable to display preview. Download preview PDF.
- 2.P. I. Fields, R. V. Swanson, C. G. Haidaris and F. Heffron, Mutants of Salmonella typhimurium that cannot survive within the macrophage are avirulent. Proc. Natl. Acad. Sci. (USA) 5189–5193 (1986).Google Scholar
- 6.B. Demple, A. Johnson and D. Fung, Exonuclease III and endonuclease IV remove 3’ blocks from DNA synthesis primers in H2O2-damaged Escherichia coli. Proc. Natl. Acad. Sci. (USA) 7731–7735 (1986).Google Scholar
- 8.R. P. Cunningham, S. M. Saporito, S. G. Spitzer and B. Weiss, An Endonuclease IV (nfo) mutant of Escherichia coli. J. Bacteriol. 168, 1120-1127 (1986).Google Scholar
- 9.S. Linn. The deoxyribonucleases of Escherichia coli. In Nucleases (S. Linn and R. J. Roberts, Eds.) pp. 291–310. Cold Spring Harbor Laboratory, New York (1985).Google Scholar
- 12.J. T. Greenberg and B. Demple, Glutathione in Escherichia coli is dispensable for resistance to H2O2 and ionizing radiation. J. Bacteriol. 169, 1026–1029 (1986).Google Scholar
- 13.I R. A. VanBogelen, P. M. Kelley and, F. C. Neidhardt, Differential induction of heat shock, SOS, and oxidation stress régulons and accumulation of nucleotides in Escherichia coli. J. Bacteriol. 169, 26–32 (1987).Google Scholar