Reductive Metabolism of Nitroaromatic and Nitropolycyclic Aromatic Hydrocarbons

  • Carl E. Cerniglia
  • Charles C. Somerville
Part of the Environmental Science Research book series (ESRH, volume 49)


Nitro-PAHs are polycyclic aromatic hydrocarbon derivatives that contain one or more nitro groups covalently bound at chemically reactive positions on the aromatic ring. Mixtures of nitrated PAHs are generated either by reactions of PAHs with nitrogen oxides or as byproducts of the incomplete combustion of fossil fuels (65). A wide variety of nitro-PAHs have been isolated from environmental sources, such as coal fly ash, diesel emission particulates, cigarette smoke and carbon black photocopier toners (29, 52, 63, 74, 75, 86, 87, 88). Structures of representative nitro-PAHs isolated from the environment are shown in Figure 1.


Polycyclic Aromatic Hydrocarbon Nitro Group Intestinal Microflora Nitroaromatic Compound Reductive Metabolism 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Anlezark, G. M., R. G. Melton, R. F. Sherwood, B. Coles, F. Friedlos, and R. Knox. 1992. The bioactivation of 5-(aziridin-l-yl)-2,4-dinitrobenzamide (CB1954)-1. Purification and properties of a nitroreductase enzyme from Escherichia coli — a potential enzyme for antibody-directed enzyme prodrug therapy (ADEPT). Biochem. Pharmacol. 44:2289–2295.PubMedCrossRefGoogle Scholar
  2. 2.
    Asnis, R. E. 1957. The reduction of furacin by cell-free extracts of furacin-resistant and parent-susceptible strains of Escherichia coli. Arch. Biochem. Biophys. 66:208–216.PubMedCrossRefGoogle Scholar
  3. 3.
    Beland, F. A., R. H. Heflich, P. C. Howard, and P. P. Fu. 1985. The in vitro metabolic activation of nitropolycyclic aromatic hydrocarbons, p. 371–396. In R. G. Harvey (ed.), Polycyclic hydrocarbons and carcinogenesis. ACS Symposium Series 283. American Chemical Society, Washington, D.C.CrossRefGoogle Scholar
  4. 4.
    Blasco, R., and F. Castillo. 1993. Characterization of a nitrophenol reductase from the phototrophic bacterium Rhodobacter capsulatus EIFI. Appl. Environ. Microbiol. 59:1774–1778.PubMedGoogle Scholar
  5. 5.
    Bryant, C., and M. DeLuca. 1991. Purification and characterization of an oxygen-insensitive NAD(P)H nitroreductase from Enterobacter cloacae. J. Biol. Chem. 266:4119–4125.PubMedGoogle Scholar
  6. 6.
    Bryant, C., and W. D. McElroy. 1991. Nitroreductases. In F. Muller (ed.), Chemistry and biochemistry of flavoenzymes — Vol. II. CRC Press, Boca Raton.Google Scholar
  7. 7.
    Bryant, C., L. Hubbard, and W. D. McElroy. 1991. Cloning, nucleotide sequence and expression of the nitroreductase gene from Enterobacter cloacae. J. Biol. Chem. 266:4126–4130.PubMedGoogle Scholar
  8. 8.
    Bryant, D. W., D. R. McCalla, M. Leeksma, and P. Laneuville. 1981. Type I nitroreductases of Escherichia coli. Can. J. Microbiol. 27:81–86.PubMedCrossRefGoogle Scholar
  9. 9.
    Bryant, D. W., D. R. McCalla, P. Lultschik, M. A. Quilliam, and B. E. McCarry. 1984. Metabolism of 1,8-dinitropyrene by Salmonella typhimurium. Chem.-Biol. Interact. 49:351–368.PubMedCrossRefGoogle Scholar
  10. 10.
    Campbell, W. L., W. Franklin, and C. E. Cerniglia. 1992. Validation studies on an in vitro semicontinuous culture system designed to simulate a bacterial ecosystem of the human intestine. J. Microbiol. Methods 16:239–252.CrossRefGoogle Scholar
  11. 11.
    Cartwright, N. J., and R. B. Cain. 1959. Bacterial degradation of nitrobenzoic acids, 2. Reduction of the nitro group. Biochem. J. 73:305–314.PubMedGoogle Scholar
  12. 12.
    Cerniglia, C. E. 1985. Metabolism of 1-nitropyrene and 6-nitrobenzo[a]pyrene by intestinal microflora, p.133–137. In B. Wostmann, J. R. Pleasants, M. Pollard, B. A. Teah and M. Wagner (ed.), Progress in clinical and biological research, Vol. 181. Germfree research; microflora control and its application to the biomedical sciences. Alan R. Liss, Inc., New York.Google Scholar
  13. 13.
    Cerniglia, C. E., P. C. Howard, P. P. Fu, and W. Franklin. 1984. Metabolism of nitropolycyclic aromatic hydrocarbons by human intestinal microflora. Biochem. Biophys. Res. Commun. 123:262–269.PubMedCrossRefGoogle Scholar
  14. 14.
    Cerniglia, C. E., J. P. Freeman, G. L. White, R. H. Heflich, and D. W. Miller. 1985. Fungal metabolism and detoxification of the nitropolycyclic aromatic hydrocarbon, 1-nitropyrene. Appl. Environ. Microbiol. 50:649–655.PubMedGoogle Scholar
  15. 15.
    Cerniglia, C. E., K. J. Lambert, G. L. White, R. H. Heflich, W. Franklin, E. K. Fifer, and F. A. Beland. 1987. Metabolism of 1,8-dinitropyrene by human, rhesus monkey and rat intestinal microflora. Toxic. Assess. Int. Q. 3:147–159.CrossRefGoogle Scholar
  16. 16.
    Cerniglia, C. E. 1992. Biodegradation of polycyclic aromatic hydrocarbons. Biodegradation 3:351–368.CrossRefGoogle Scholar
  17. 17.
    Cerniglia, C. E. 1993. Biodegradation of polycyclic aromatic hydrocarbons. Curr. Opin. Biotechnol. 4:331–338.CrossRefGoogle Scholar
  18. 18.
    Cerniglia, C. E., J. B. Sutherland, and S. A. Crow. 1992. Fungal metabolism of aromatic hydrocarbons, p. 193–217. In G. Winkelmann (ed.) Microbial degradation of natural products. VCH Verlagsgesellschaft, Weinheim.Google Scholar
  19. 19.
    Chadwick, R. W., S. E. George, and L. R. Claxton. 1992. Role of gastrointestinal mucosa and microflora in the bioactivation of dietary and environmental mutagens or carcinogens. Drug Metab. Rev. 24:425–492.PubMedCrossRefGoogle Scholar
  20. 20.
    Delclos, K. B., C. E. Cerniglia, K. L. Dooley, W. L. Campbell, W. Franklin, and R. P. Walker. 1989. The role of intestinal microflora in the metabolic activation of 6-nitrochrysene to DNA-binding derivatives in mice. Toxicology 60:137–150.CrossRefGoogle Scholar
  21. 21.
    Doi, T., H. Yoshimura, and K. Tatsumi. 1983. Properties of nitrofuran reductases from Escherichia coli B/r. Chem. Pharm. Bull. 31:1105–1107.PubMedCrossRefGoogle Scholar
  22. 22.
    Doolittle, D. J., J. M. Sherrill, and B. E. Butterworth. 1983. Influence of intestinal bacteria, sex of the animal, and position of the nitro group on the hepatic genotoxicity of nitrotoluene isomers in vivo. Cancer Res. 43:2836–2842.PubMedGoogle Scholar
  23. 23.
    Drasar, B. S., and B. I. Duerden. 1991. Anaerobes in the normal flora of man, p. 162–179. In B. I. Duerden and B. S. Drasar (ed.), Anaerobes in human disease. Wiley-Liss, New York.Google Scholar
  24. 24.
    Egami, F., H. Ebata, and R. Sato. 1951. Reduction of chloromycetin by a cell-free bacterial extract and its relation to nitrite reduction. Nature 167:118–119.PubMedCrossRefGoogle Scholar
  25. 25.
    El-Bayoumy, K., C. Sharma, Y. M. Louis, B. Reddy, and S. S. Hecht. 1983. The role of intestinal microflora in the metabolic reduction of 1-nitropyrene to 1-aminopyrene in conventional and germ free rats and in humans. Cancer Lett. 19:311–316.PubMedCrossRefGoogle Scholar
  26. 26.
    Fu, P. P., M. W. Chou, D. W. Miller, G. L. White, R. H. Heflich, and F. A. Beland. 1985. The orientation of the nitro substituent predicts the direct-acting bacterial mutagenicity of nitrated polycyclic aromatic hydrocarbons. Mutat. Res. 143:173–181.PubMedCrossRefGoogle Scholar
  27. 27.
    Fu, P. P., C. E. Cerniglia, K. E. Richardson, and R. H. Heflich. 1988. Nitroreduction of 6-nitrobenzo[a]pyrene in humans. Mutat. Res. 209:123–129.PubMedCrossRefGoogle Scholar
  28. 28.
    Fu, P. P. 1990. Metabolic activation of nitro-polycyclic aromatic hydrocarbons. Drug Metab. Rev. 22:209–268.PubMedCrossRefGoogle Scholar
  29. 29.
    Gibson, T. L. 1983. Sources of direct-acting nitroarene mutagens in airborne particulate matter. Mutat. Res. 122:115–121.PubMedCrossRefGoogle Scholar
  30. 30.
    Groenewegen, P. E. J., P. Breeuwer, J. M. L. M. van Helvoort, A. A. M. Langenhoff, F. P. de Vries, and J. A. M. de Bont. 1992. Novel degradative pathway of 4-nitrobenzoate in Comamonas acidovorans NBA-10. J. Gen. Microbiol. 138:1599–1605.PubMedCrossRefGoogle Scholar
  31. 31.
    Heflich, R. H., E. K. Fifer, Z. Djuri, and F. A. Beland. 1985. DNA adduct formation and mutation induction by nitropyrenes in Salmonella and Chinese hamster ovary cells: relationships with nitroreduction and acetylation. Environ. Health Perspect. 62:135–143.PubMedCrossRefGoogle Scholar
  32. 32.
    Heflich, R. H., Z. Djuri, E. K. Fifer, C. E. Cerniglia, and F. A. Beland. 1986a. Metabolism of dinitropyrenes to DNA-binding derivatives in vitro and in vivo, p. 185–197. In N. Ishinishi, A. Koizumi, R. O. McClellan, and W. Stîber (ed.), Carcinogenic and mutagenic effects of diesel engine exhaust. Elsevier, Amsterdam.Google Scholar
  33. 33.
    Heflich, R.H., E.K. Fifer, Z. Djuri, and F.A. Beland. 1986b. Mutation induction and DNA adduct formation by 1,8-dinitropyrene in Chinese hamster ovary cells, p. 265–273. In C. Ramel, R. Lambert, and J. Monson (ed.), Genetic toxicology of environmental chemicals, Part A: Basic principles and mechanisms of action. Alan R. Liss, New York.Google Scholar
  34. 34.
    Heflich, R. H., P. C. Howard, and F. A. Beland. 1985. 1-Nitrosopyrene: an intermediate in the metabolic activation of 1-nitropyrene to a mutagen in Salmonella typhimurium TA1538. Mutat. Res. 149:25–32.PubMedCrossRefGoogle Scholar
  35. 35.
    Heitkamp, M. A., and C. E. Cerniglia. 1988. Mineralization of polycyclic aromatic hydrocarbons by a bacterium isolated from sediments below an oil field. Appl. Environ. Microbiol. 54:1612–1614.PubMedGoogle Scholar
  36. 36.
    Heitkamp, M. A., J. P. Freeman, D. W. Miller, and C. E. Cerniglia. 1991. Biodegradation of 1-nitropyrene. Arch. Microbiol. 156:223–230.PubMedCrossRefGoogle Scholar
  37. 37.
    Howard, P. C., F. A. Beland, and C. E. Cerniglia. 1983. Reduction of 1-nitropyrene to 1-aminopyrene by rat intestinal bacteria. Carcinogenesis 4:985–990.PubMedCrossRefGoogle Scholar
  38. 38.
    Howard, P. C., R. H. Heflich, F. E. Evans, and F. A. Beland. 1983. Formation of DNA adducts in vitro and in Salmonella typhimurium upon metabolic reduction of the environmental mutagen 1-nitropyrene. Cancer Res. 43:2052–2058.PubMedGoogle Scholar
  39. 39.
    IARC. 1984. IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans, p. 171–178. Vol. 33. Polynuclear aromatic compounds, Part 2. Carbon blacks, mineral oils and some nitroarenes. IARC, Lyon.Google Scholar
  40. 40.
    IARC. 1989. IARC Monographs on the Evaluation of the Carcinogenic Risks to Humans, p. 31–458. Vol. 46. Diesel and gasoline engine exhausts and some nitroarenes. IARC, Lyon.Google Scholar
  41. 41.
    Jung, H., A. U. Shaikh, R. H. Heflich, and P. P. Fu. 1991. Nitro group orientation, reduction potential, and direct-acting mutagenicity of nitro-polycyclic aromatic hydrocarbons. Environ. Mol. Mutagen. 17:169–180.PubMedCrossRefGoogle Scholar
  42. 42.
    Kinouchi, T., Y. Manabe, K. Wakisaki, and Y. Ohnishi. 1982. Biotransformation of 1-nitropyrene in intestinal anaerobic bacteria. Microbiol. Immunol. 26:992–1005.Google Scholar
  43. 43.
    Kinouchi, T., and Y. Ohnishi. 1983. Purification and characterization of 1-nitropyrene reductases from Bacteroides fragilis. Appl. Environ. Microbiol. 46:596–604.PubMedGoogle Scholar
  44. 44.
    Kinouchi, T., and Y. Ohnishi. 1986. Metabolic activation of 1-nitropyrene and 1,6-dinitropyrene by nitroreductases from Bacteroides fragilis and distribution of nitroreductase activity in rats. Microbiol. Immunol. 30:979–992.PubMedGoogle Scholar
  45. 45.
    Kinouchi, T., K. Nishifuji, and Y. Ohnishi. 1987. In vitro intestinal microflora-mediated metabolism of biliary metabolites from 1-nitropyrene-treated rats. Microbiol. Immunol. 31:1145–1159.PubMedGoogle Scholar
  46. 46.
    Manning, B. W., C. E. Cerniglia, and T. W. Federle. 1986. Biotransformation of 1-nitropyrene to 1-aminopyrene and N-formyl-l-aminopyrene by the human intestinal microbiota. Toxicol. Environ. Health 18:339–346.CrossRefGoogle Scholar
  47. 47.
    Manning, B. W., W. C. Campbell, W. Franklin, K. B. Delclos, and C. E. Cerniglia. 1988. Metabolism of 6-nitrochrysene by intestinal microflora. Appl. Environ. Microbiol. 34:197–203.Google Scholar
  48. 48.
    Manning, B. W., T. W. Federle, and C. E. Cerniglia. 1987. Use of a semi-continuous culture system as a model for determining the role of human intestinal microflora in the metabolism of xenobiotics. J. Microbiol. Methods 6:81–94.CrossRefGoogle Scholar
  49. 49.
    Mason, R. P., and J. L. Holtzman. 1975. The role of catalytic Superoxide formation in the O2 inhibition of nitroreductase. Biochem. Biophys. Res. Commun. 67:1267–1274.PubMedCrossRefGoogle Scholar
  50. 50.
    Mattammal, M. B., T. V. Zenser, M. O. Palmier, and B. B. Davis. 1985. Renal reduced nicotinamide adenine dinucleotide phosphate: cytochrome c reductase-mediated metabolism of the carcinogen 7V-[4-(5-nitro-2-furyl)-2-thiazolyl]acetamide. Cancer Res. 45:149–156.PubMedGoogle Scholar
  51. 51.
    McCann, J., E. Choi, E. Yamasaki, and B. N. Ames. 1975. Detection of carcinogens as mutagens in the Salmonella microsome test: assay of 300 chemicals. Proc. Natl. Acad. Sci. USA 72:5135–5139.PubMedCrossRefGoogle Scholar
  52. 52.
    McCartney, M. A., B. F. Chatterjee, E. C. McCoy, E. A. Mortimer, Jr., and H. S. Rosenkranz. 1986. Airplane emissions: a source of mutagenic nitrated polycyclic aromatic hydrocarbons. Mutat. Res. 171:99–104.PubMedCrossRefGoogle Scholar
  53. 53.
    McCoy, E. C., H. S. Rosenkranz, and P. C. Howard. 1990. Salmonella typhimurium TA100Tn5-1012, a strain deficient in arylhydroxylamine O-esterificase, exhibits a reduced nitroreductase activity. Mutat. Res. 243:141–144.PubMedCrossRefGoogle Scholar
  54. 54.
    McCoy, E. C., H. S. Rosenkranz, and R. Mermelstein. 1981. Evidence for the existence of a family of bacterial nitroreductases capable of activating nitrated polycyclics to mutagens. Environ. Mutagen. 3:421–437.PubMedCrossRefGoogle Scholar
  55. 55.
    Mermelstein, R., D. K. Kiriazides, M. Butler, E. C. McCoy, and H. S. Rosenkranz. 1981. The extraordinary mutagenicity of nitropyrenes in bacteria. Mutat. Res. 89:187–196.PubMedCrossRefGoogle Scholar
  56. 56.
    Messier, F., C. Lu, P. Andrews, B. E. McCarry, M. A. Quilliam, and D. R. McCalla. 1981. Metabolism of 1-nitropyrene and formation of DNA adducts in Salmonella typhimurium. Carcinogenesis 2:1007–1011.PubMedCrossRefGoogle Scholar
  57. 57.
    Millner, G. C., and C. E. Cerniglia. 1986. Microbial transformation and detoxification of 6-ni-trobenzo[a]pyrene. Toxicol. Environ. Health 19:519–530.CrossRefGoogle Scholar
  58. 58.
    Mirsalis, J. C., T. E. Hamm, J. M. Sherrill, and B. E. Butterworth. 1982. Role of gut flora in genotoxicity of dinitrotoluene. Nature 295:322–323.PubMedCrossRefGoogle Scholar
  59. 59.
    Mîller, L., M. Corrie, T. Midtvedt, J. Rafter, and J.-A. Gustafsson. 1988. The role of the intestinal microflora in the formation of mutagenic metabolites from the carcinogenic air pollutant 2-nitrofluorene. Carcinogenesis 9:823–830.CrossRefGoogle Scholar
  60. 60.
    Morehead, M. C., W. Franklin, P. P. Fu, F. E. Evans, T. M. Heinze, and C. E. Cerniglia. 1994. Metabolism of 7-nitrobenz[a]anthracene by intestinal microflora. J. Toxicol. Environ. Health (In press).Google Scholar
  61. 61.
    Narai, N., S. Kitamura, and K. Tatsumi. 1984. A comparative study on 1-nitropyrene and nitrofurazone reductases in Escherichia coli. J. Pharm. Dyn. 7:407–413.CrossRefGoogle Scholar
  62. 62.
    Nishino, S. F., and J. C. Spain. 1993. Degradation of nitrobenzene by a Pseudomonas pseudoalcaligenes. Appl. Environ. Microbiol. 59:2520–2525.PubMedGoogle Scholar
  63. 63.
    Ohnishi, Y, T. Kinouchi, Y. Manabe, H. Tsutsui, H. Otsuka, H. Tokiwa, and T. Otofuji. 1985. Nitro compounds in environmental mixtures and foods, p. 195–204. In M. D. Waters, S. S. Sandhu, J. Lewtas, L. Claxton, G. Strauss, and S. Nesnow (ed.), Short-term bioassays in the analysis of complex environmental mixtures. Vol. IV. Plenum Publishing Corporation, New York.CrossRefGoogle Scholar
  64. 64.
    Peterson, F. J., R. P. Mason, J. Hovespian, and J. L. Holtzman. 1979. Oxygen-sensitive and-insensitive nitroreduction by Escherichia coli and rat hepatic microsomes. J. Biol. Chem. 254:4009–4014.PubMedGoogle Scholar
  65. 65.
    Pitts, J. N., Jr., K. A. Van Cauwenberghe, D. Grosjean, J. P. Schmid, D. R. Fitz, W. L. Belser, Jr., G. B. Knudson, and P. M. Hynds. 1978. Atmospheric reactions of polycyclic aromatic hydrocarbons: facile formation of mutagenic nitro derivatives. Science 202:515–518.PubMedCrossRefGoogle Scholar
  66. 66.
    Pothuluri, J. V., F. E. Evans, T. M. Heinze, and C. E. Cerniglia. 1994. Metabolism of 3-nitrofluoranthene, a nitropolycyclic aromatic hydrocarbon, by the fungus Cunninghamella elegans. J. Toxicol. Environ. Health 42:209–218.PubMedCrossRefGoogle Scholar
  67. 67.
    Preuss, A., J. Fimpel, and G. Diekert. 1993. Anaerobic transformation of 2,4,6-trinitrotoluene (TNT). Arch. Microbiol. 159:345–353.PubMedCrossRefGoogle Scholar
  68. 68.
    Rafii, F., W. Franklin, R. H. Heflich, and C. E. Cerniglia. 1991. Reduction of nitroaromatic compounds by anaerobic bacteria isolated from the human gastrointestinal tract. Appl. Environ. Microbiol. 57:962–968.Google Scholar
  69. 69.
    Rafii, F., and C. E. Cerniglia. 1993. Comparison of the azoreductase and nitroreductase from Clostridium perfringens. Appl. Environ. Microbiol. 59:1731–1734.PubMedGoogle Scholar
  70. 70.
    Rafii, F., A. L. Selby, R. K. Newton, and C. E. Cerniglia. Reduction and mutagenic activation of nitroaromatic compounds by a Mycobacterium sp. Appl. Environ. Microbiol. 60:4263-4267.Google Scholar
  71. 71.
    Reddy, B. G., L. R. Pohl, and G. Krishna. 1976. The requirement of the gut flora in nitrobenzene-induced methemoglobinemia in rats. Biochem. Pharmacol. 25:1119.PubMedCrossRefGoogle Scholar
  72. 72.
    Richardson, K. E., P. P. Fu, and C. E. Cerniglia. 1988. Metabolism of 1-, 3-, and 6-nitrobenzo[a]pyrene by intestinal microflora. J. Toxicol. Environ. Health 23:527–537.PubMedCrossRefGoogle Scholar
  73. 73.
    Rickert, D. E., Butterworth, B. E., and J. A. Popp. 1984. Dinitrotoluene: Acute toxicity, oncogenicity, genotoxicity, and metabolism. CRC Crit. Rev. Toxicol. 13:217–234.CrossRefGoogle Scholar
  74. 74.
    Rosenkranz, H. S., and D. R. Sanders. 1980. Nitropyrenes: isolation, identification, and reduction of mutagenic impurities in carbon black toners. Science 209:1039–1043.PubMedCrossRefGoogle Scholar
  75. 75.
    Rosenkranz, H. S. 1982. Direct-acting mutagens in diesel exhausts: magnitude of the problem. Mutat. Res. 101:1–10.PubMedCrossRefGoogle Scholar
  76. 76.
    Rosenkranz, H. S., and R. Mermelstein. 1983. Mutagenicity and genotoxicity of nitroarenes. All nitrocontaining chemicals were not created equal. Mutat. Res. 114:217–267.PubMedCrossRefGoogle Scholar
  77. 77.
    Rowland, I. R. 1988. Factors affecting metabolic activity of the intestinal flora. Drug Metab. Rev. 19:243–262.PubMedCrossRefGoogle Scholar
  78. 78.
    Saz, A. K., and J. Marmur. 1953. The inhibition of organic nitro-reductase by aureomycin in cell-free extracts. Proc. Soc. Exp. Biol. Med. 82:783–784.PubMedGoogle Scholar
  79. 79.
    Saz, A. K., and M. L. Martinez. 1956. Enzymatic basis of resistance to aureomycin I. Differences between flavoprotein reductases of sensitive and resistant Escherichia coli. J. Biol. Chem. 223:285–292.PubMedGoogle Scholar
  80. 80.
    Saz, A. K. and R. B. Slie. 1954. Reversal of aureomycin inhibition of bacterial cell-free nitro reductase by manganese. J. Biol. Chem. 210:407–412.PubMedGoogle Scholar
  81. 81.
    Saz, A. K., and R. B. Slie. 1954. The inhibition of organic nitro reductase by aureomycin in cell-free extracts II. Cofactor requirements for the nitro reducíase enzyme complex. Arch. Biochem. Biophys. 51:5–16.PubMedCrossRefGoogle Scholar
  82. 82.
    Smith, G. N., and C. S. Worrel. 1949. Enzymatic reduction of chloramphenicol (chloromycetin). Arch. Biochem. 24:216–223.PubMedGoogle Scholar
  83. 83.
    Somerville, C. C., S. F. Nishino, and J. C. Spain. Isolation and characterization of nitrobenzene nitroreductase from Pseudomonas pseudoalcaligenes JS45. J. Bacteriol. (In press).Google Scholar
  84. 84.
    Tatsumi, K., T. Doi, H. Yoshimura, H. Koga, and T. Horiuchi. 1982. Oxygen-insensitive nitrofuran reductases in Salmonella typhimurium TA 100. J. Pharm. Dyn. 5:423–429.CrossRefGoogle Scholar
  85. 85.
    Thornton-Manning, J. R., W. L. Campbell, B. S. Hass, J. J. Chen, P. P. Fu, C. E. Cerniglia, and R. H. Heflich. 1989. The role of nitro-reduction in the synergistic mutational response induced by mixtures of 1-and 3-nitrobenzo[a]pyrene in Salmonella typhimurium. Environ. Mol. Mutagen. 13:203–210.PubMedCrossRefGoogle Scholar
  86. 86.
    Tokiwa, H., and Y. Ohnishi. 1986. Mutagenicity and carcinogenicity of nitroarenes and their sources in the environment. CRC Crit. Rev. Toxicol. 17:23–60.CrossRefGoogle Scholar
  87. 87.
    Tokiwa, H., T. Otofugi, R. Nakagawa, K. Horikawa, T. Maeda, N. Sano, K. Izumi, and H. Otsuka. 1986. Dinitro derivatives of pyrene and fluoranthene in diesel emission particulates and their tumorigenicity in mice and rats. Dev. Toxicol. Environ. Sci. 13:253–270.PubMedGoogle Scholar
  88. 88.
    Tokiwa, H., R. Nakagawa, K. Horikawa, and A. Ohkubo. 1987. The nature of the mutagenicity and carcinogenicity of nitrated aromatic compounds in the environment. Environ. Health Perspect. 73:191–199.PubMedCrossRefGoogle Scholar
  89. 89.
    Villanueva, J. R. 1964. The purification of a nitro-reductase from Nocardia V. J. Biol. Chem. 239:773–776.PubMedGoogle Scholar
  90. 90.
    Watanabe, M., M. Ishidate, Jr., and T. Nohmi. 1989. A sensitive method for the detection of mutagenic nitroarenes: construction of nitroreductase-overproducing derivatives of Salmonella typhimurium strains TA98 and TA 100. Mutat. Res. 216:211–220.PubMedCrossRefGoogle Scholar
  91. 91.
    Watanabe, M., M. Ishidate, Jr., and T. Nohmi. 1990. Nucleotide sequence of Salmonella typhimurium nitroreductase gene. Nucleic Acids Res. 18:1059.PubMedCrossRefGoogle Scholar
  92. 92.
    Watanabe, M., T. Nohmi, and M. Ishidate, Jr. 1987. New tester strains of Salmonella typhimurium highly sensitive to mutagenic nitroarenes. Biochem. Biophys. Res. Commun. 147:974–979.PubMedCrossRefGoogle Scholar
  93. 93.
    Woese, C. R. 1987. Bacterial evolution. Microbiol. Rev. 51:221–271.PubMedGoogle Scholar
  94. 94.
    Yamashina, I. 1954. Enzymatic reduction of aromatic nitro compounds. Bull. Chem. Soc. Japan 27:85–89.CrossRefGoogle Scholar
  95. 95.
    Yamashina, I., S. Shikata, and F. Egami. 1954. Enzymatic reduction of aromatic nitro, nitroso and hydroxyl amino compounds. Bull. Chem. Soc. Japan 27:42–45.CrossRefGoogle Scholar
  96. 96.
    Zenno, S., S. Inouye, and H. Kanoh. 1993. Gene encoding enzyme having flavin reducing activity and nitroreductase activity. European Patent Application no. 0 547 876 Al.Google Scholar

Copyright information

© Springer Science+Business Media New York 1995

Authors and Affiliations

  • Carl E. Cerniglia
    • 1
  • Charles C. Somerville
    • 2
  1. 1.National Center for Toxicological ResearchU.S. Food and Drug AdministrationJeffersonUSA
  2. 2.Armstrong LaboratoryU.S. Air ForceUSA

Personalised recommendations