Potent Intracellular Oxidative Stress Exerted by the Carcinogen 4-Nitroquinoline- N-oxide Tatsuo Nunoshiba and Bruce Demple Cancer Res 1993;53:3250-3252. Published online July 1, 1993.
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ICANCER RESEARCH 53. 3250-3252. July 15. 1993|
Advances in Brief
Potent Intracellular Oxidative Stress Exerted by the Carcinogen 4-Nitroquinoline-A^-oxide1 Tatsuo Nunoshiba and Bruce Demple2 Department of Molecular and Cellular Toxicology. Harvard School of Public Health. Boston. Massachusetts
tory system of E. coli. This 4NQO-induced oxidative stress might contribute to the tumor-promoting activity of 4NQO.
Abstract Oxidative
02115
stress
exerted
by superoxide-generating
(redox-cycling)
agents such as paraquat triggers the soxRS regulon of Escherichia coli. In this system, SoxR protein is the redox-sensitive activator of the soxS gene, the product of which then activates the —¿10 promoters of this regulon. We found that 4-nitroquinoline-iV-oxide (4NQO) is a powerful inducer of soxS, > 10-fold more potent than paraquat. The transcriptional induction of the soxS gene by 4NQO was tightly dependent on a functional soxR gene and on the presence of molecular oxygen, as found previously for several well characterized redox-cycling agents. Two 4NQO-related compounds were also shown to induce sinhibition of nitroreductase. Biochem. Biophys. Res. Commun., 67: 1267-1274. 1975. 19. Wardman. P., and Clarke. E. D. Oxygen inhibition of nitroreductase: electron transfer from nitro radical-anions to oxygen. Biochem. Biophys. Res. Commun.. 69: 942-949, 1976. 20. Sealy, R. C., Swartz, H. M.. and Olive, P. L. Electron spin resonance-spin trapping. Detection of Superoxide formation during aerobic microsomal reduction of nitrocompounds. Biochem. Biophys. Res. Commun.. «2:680-684, 1978. 21. Biaglow. J. E., Jacobson, B. E., and Nygaard, O. F. Metabolic reduction of 4-nitroquinoline-iV-oxide and other radical-producing drugs to oxygen-reactive intermedi ates. Cancer Res., 37: 3306-3313, 1977. 22. Demple, B, and Levin, J. D. Repair systems for radical-damaged DNA. In: H. Sies (ed.), Oxidative Stress: Oxidants and Antioxidants, pp. 119-154. London: Academic Pressine., 1991. 23. Greenberg, J. T, and Demple, B. A global response induced in Escherichia coli by redox-cycling agents overlaps with that induced by peroxide stress. J. Bacteriol., 171: 3933-3939, 1989. 24. Nettleton, C. J.. Bull. C.. Baldwin. T. O., and Fee, J. A. Isolation of the Escherichia coli iron Superoxide dismutase gene: evidence that intracellular Superoxide concen tration does not regulate oxygen-dependent synthesis of the manganese Superoxide dismutase. Proc. Nati. Acad. Sci. USA, 81: 4970-4973, 1984. 25. Touati. D. Transcriptional and posttanscriptional regulation of manganese Superoxide dismutase biosynthesis in Escherichia coli, studied with operon and protein fusions. J. Bacteriol., 770: 2511-2520, 1988. 26. Liochev, S. I., and Fridovich, I. Fumarase C. the stable fumarase of Eschrichia coli, is controlled by the soxRS regulon. Proc. Nati. Acad. Sci. USA, 89: 5892-5896, 1992. 27. Imlay, J.. and Fridovich, I. Exogenous quiñonesdirectly inhibit the respiratory NADH dehydrogenase in Escherichia coli. Arch. Biochem. Biophys., 296: 337-346, 1992. 28. Kohda, K., Tada, M., Kasai, H., Nishimura, S., and Kawazoe, Y. Formation of 8-hydroxyguanine residues in cellular DNA exposed to the carcinogen 4-nitroquino line-l-oxide. Biochem. Biophys. Res. Commun.. 139: 626-632. 1986. 29. Demple. B., Johnson, A, and Fung, D. Exonuclease III and endonuclease IV remove 3' blocks from DNA synthesis primers in H^Oi-damaged Escherichia coli. Proc. Nati. Acad. Sci. USA, 83: 7731-7735. 1986. 30. Murrell, G. A. C.. Francis, M. J. O., and Bromley. L. Modulation of fibroblast proliferation by oxygen free radicals. Biochem. J., 265: 659-665, 1990. 31. Burdon. R. H., Gill, V, and Rice-Evans, C. Oxidative stress and tumor cell prolifer ation. Free Radical Res. Commun., //: 65-76, 1990.
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