Advertisement

Nitroarenes pp 39-59 | Cite as

In Vivo Metabolism and Genotoxic Effects of the Air Pollutant and Marker for Nitro-Pah’s, 2-Nitrofluorene

  • L. Möller
  • J. Rafter
  • S. Törnquist
  • L. Eriksson
  • B. Beije
  • R. Toftgård
  • T. Midvedt
  • M. Corrie
  • J-Å Gustafsson
Part of the Environmental Science Research book series (ESRH, volume 40)

Abstract

During incomplete combustion of organic matter there is a formation of polycyclic aromatic hydrocarbons (PAH) which can react with oxides of nitrogen, with the formation of nitro-PAH’s as a result, a reaction which is catalyzed by a low pH. 2-Nitrofluorene (NF), a marker for nitro-PAH, is in vivo metabolized via two different routes. After inhalation there is a formation of potent mutagenic metabolites, ON-NF’s, which are distributed in the body. After oral administration, NF is reduced to the amine, a reaction mediated by the intestinal microflora, and further acetylated to 2-acetylaminofluorene (AAF), a potent carcinogen. Further ringhydroxylation of AAF leads to detoxification and excretion.

Induction of cytochrome P450 c,d affects the metabolism in that more OH-NF’s are formed. As a consequence, more mutagenic metabolites are found in the circulation. The liver excretes OH-NF’s as, in terms of mutagenicity, totally harmless glucuronide conjugates. When these conjugates are excreted via the bile, intestinal beta-glucuronidase can liberate direct-acting mutagens in the intestine. Thus, inhalation of NF can lead to formation of potent mutagens in the intestine.

NF induces DNA-repair, in vivo, and is an initiatior and a weak promotor, measured as formation of preneoplastic lesions in the liver. Risk estimates, by two different methods, indicate that nitro-PAH’s extrapolated from the marker NF, can expose humans to a cancer risk on a non-neglectable level.

Keywords

Polycyclic Aromatic Hydrocarbon Diesel Exhaust Sister Chromatid Exchange Intestinal Microflora Preneoplastic Lesion 
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.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Lindvall, T. (1985). Health effects of nitrogen dioxide and oxidants. Stand. J Work Environ. Health. 11, 10–28.Google Scholar
  2. 2.
    Tokiwa, H., Nakagawa, R, Morita, K. and Ohnishi, Y. (1981). Mutagenicity of nitro derivatives induced by exposure of aromatic compounds to nitrogen dioxide., Mutat. Res., 85, 195.CrossRefPubMedGoogle Scholar
  3. 3.
    McCoy, E. (1984). Role of metabolism on the mutagenicity of nitroarenes. In: Biochemical Basis of Chemical Carcinogenesis, Eds., Greim, H., Jung, M. Kramer, M., Marquardt, H. and Oesch, F. Raven Press, New York, p57.Google Scholar
  4. 4.
    Danford, N., Wilcox, P. and Parry, J.M. (1982). The clastogenic activity of dinitropyrenes in a rat liver epithelial cell line. Mutat. Res. 105, 349.CrossRefPubMedGoogle Scholar
  5. 5.
    Nachtman, J.P. and Wolff, S. (1982). Activity of nitro-polynuclear aromatic hydrocarbons in the sister chromatide exchange assay with and without metabolic activation. Environ. Mutagen. 4,1.CrossRefPubMedGoogle Scholar
  6. 6.
    Neal, S.B. and Probst G.S. (1983). Chemically-induced sister chromatid exchange in vivo In bone marrow of Chinese hamsters, an evaluation of 24 compounds. Mutat. Res. 113, 33.CrossRefPubMedGoogle Scholar
  7. 7.
    Tucker, J.D. and Ong, T. (1984). Induction of sister chromatid exchanges and chromosome aberrations in human peripheral lymphocytes by 2,4,7-trinitro-9-fluorene. Mutat, Res. 138, 181.CrossRefGoogle Scholar
  8. 8.
    Hartong, A., Kraft, J., Schulze, J., Kiess, H. and Lies, K-H. (1984). The identification of nitrated polycyclic aromatic hydrocarbons in diesel particulate extracts and their potential formation as artifacts during particulate collection. Chromatographia, 19, 269–273.CrossRefGoogle Scholar
  9. 9.
    Handa, T., Yamauchi, T., Ohnishi, M., Hisematsu, Y. and Ishii, T. (1983). Detection and average content levels of carcinogenic and mutagenic compounds from the particulates on diesel and gasoline engine muffers. Environ. International, 9, 335–341.CrossRefGoogle Scholar
  10. 10.
    Tokiwa, H., Nakagawa, R and Horikowa, H. (1985). Mutagenic/carcinogenic agents in indoor pollutants: The dinitropyrenes generated by kerosene heaters and fuel gas and liquified petroleum gaś burners. Mutat. Res., 157, 39–47.CrossRefPubMedGoogle Scholar
  11. 11.
    Ramdahl, T., Becher, G. and Bjtirseth, A. (1982). Nitrated polycyclic aromatic hydrocarbons in urban air particles. Environ. Sci. Technol. 16, 861–865.CrossRefPubMedGoogle Scholar
  12. 12.
    Gorse, RA., Riley, T.L., Ferris, F.C., Pero, A.M. and Skewes, L.M. (1983). 1-Nitropyrene concentration and bacterial mutagenicity in on-road vehicle emissions. Environ. Sci. Technol. 17, 198–202.CrossRefPubMedGoogle Scholar
  13. 13.
    Tokiwa, H., Kitamori, S., Nakagawa, R and Ohnishi, Y. (1983). Mutagens in airborne particulate pollutants and nitro derivatives produced by exposure of aromatic compounds to gaseous pollutants. Environ. Sci. Res. 27, 555–567.Google Scholar
  14. 14.
    Moriske, H.-J. (1986). Polare verbindungen im Stadtaerosol. VDI Fortschrittberichte, Reike 15, no. 42, VDI-Verlag, Düsseldorf.Google Scholar
  15. 15.
    Sato, T., Kato, K., Ose, Y., Nagase, H. and Ishikawa, T. (1985). Nitroarenes in Suimon river sediment. Mutat. Res. 157, 135–143.CrossRefPubMedGoogle Scholar
  16. 16.
    Ohnishi, Y., Kinouchi, T., Manabe Y., Tsushi, H., Otsuka, H., Tokiwa, H. and Otofujil, T. (1985). Nitro compounds in environmental mixtures and foods, in short-term bioassays in the analysis of complex environmental mixtures IV, Waters, M.D. et al., eds. Plenum Press, New York, 195.CrossRefGoogle Scholar
  17. 17.
    Kinouchi, T., Hideshi, T. and Ohnishi, Y. (1986). Detection of 1-nitropyrene in Yakatori (grilled chicken). Mutat. Res. 171, 105–113.CrossRefPubMedGoogle Scholar
  18. 18.
    Tokiwa, H., Nakagawa, R, Morita, K. and Ohnishi, Y. (1981). Mutagenicity of nitro derivatives induced by exposure of aromatic compounds to nitrogen dioxide. Mutat. Res. 85, 195–205.CrossRefPubMedGoogle Scholar
  19. 19.
    Okinaka, R.T., Nichols, J.W., Whaley, T.W. and Strniste, G.F. (1984). Phototransformation of 2-aminofluorene into N-oxidized mutagens. Carciriogenesis 5, 1741–1743.CrossRefGoogle Scholar
  20. 20.
    Ohe, T. (1984). Mutagenicity of photochemical reaction products of polycyclic aromatic hydrocarbons with nitrite. The Science of the Total Environ. 39, 161–175.CrossRefGoogle Scholar
  21. 21.
    Rosenkranz, H.S., and Mermelstein, R.M. (1985). The genotoxicity, metabolism and carcinogenicity of nitrated polycyclic hydrocarbons. J. Environ. Sci. Health, 2, 221–272.Google Scholar
  22. 22.
    Tokiwa, H., Nakagawa, R. and Ohnishi Y. (1981). Mutagenic assay of aromatic nitro compounds with Salmonella typhimurium. Mutat. Res. 91, 321.CrossRefPubMedGoogle Scholar
  23. 23.
    Pitts, J.N Jr, Harger, W., Lokensgaard, D.M., Fitz, D.R, Scorziell, G.M. and Mejia, V. (1982). Diurnal variations in the mutagenicity of airborne particulate organic matter in Californias south coast air basin. Mutat. Res. 104, 35.CrossRefPubMedGoogle Scholar
  24. 24.
    Wang, Y.I.Y., Rappaport S.M., Sawyer, R.F., Talcott, R.E. and Wei, E.T. (1978). Direct-acting mutagens in automobile exhaust. Cancer Lett. 5, 39.CrossRefPubMedGoogle Scholar
  25. 25.
    Pederson, T.C. and Siak, J-S. (1981). The role of nitroaromatic compounds in the direct acting mutagenicity of diesel particle extracts. J. Appl. Toxicol. 1, 54.CrossRefPubMedGoogle Scholar
  26. 26.
    El-Bayoumy, K., Hecht, S. and Holfman D. (1982). Comparative tumor initiating activity on mouse skin of 6-nitrobenzo(a)pyrene, 6-nitrochrysene, 3-nitroperylene, 1-nitropyrene and their parent hydrocarbons. Cancer Lett. 16,333.CrossRefPubMedGoogle Scholar
  27. 27.
    Miller, J.A., Sandin, R.B., Miller E.C. and Rush, H.P. (1955). The carcinogenicity of compounds related to 2-acetylaminofluorene. Cancer Res. 15, 188.PubMedGoogle Scholar
  28. 28.
    Schuetzle, D., Riley, T.L., Prater, T.J., Harvey, T.M. and Hunt, D.F. (1982). Analysis of nitrated polycyclic aromatic hydrocarbons in diesel particulate. Anal. Chem. 54, 265–271.CrossRefGoogle Scholar
  29. 29.
    Henderson, T.R, Royer, RE., Clark, C.R, Harvey, T.M. and Hunt, D.F. (1982). MS/MS analysis of diesel emissions and fuels treated with NO2. J. Appl. Toxicol. 2, 231–237.CrossRefPubMedGoogle Scholar
  30. 30.
    Schuetzle, D. (1983). Sampling of vehicle emissions for chemical analysis and biological testing. Environ. Health Perspec. 47, 65–80.CrossRefGoogle Scholar
  31. 31.
    Xu, X., Nachtman, J., Rappaport, S. and Wei, E. (1981). Identification of 2-nitrofluorene in diesel exhaust particulates. J. Appl. Toxicol. 1, 196–198.CrossRefPubMedGoogle Scholar
  32. 32.
    Nishioka, M.G., Petersen, B. and Lewtas, J. (1983). Comparison of nitro-aromatic content and direct-acting mutagenicity of passenger car engine emissions. In: Mobile Source Emissions Including Polycyclic Organic Species, Ed., Rondial, D., D. Riedel Publishing Company, p197.Google Scholar
  33. 33.
    Thorgelrsson, S.S., Weisburger, E.K, King, C.M. and Scribner, J.D. (1979). National Cancer Institute Monograph, no. 58.Google Scholar
  34. 34.
    Beije, B. and Möller, L. (1988). 2-Nitrofluorene and related compounds. Prevalence and biological effects., Mutat. Res. 196,177–209.CrossRefPubMedGoogle Scholar
  35. 35.
    Schuetzle, D. and Frazier, J.A. (1986). Factors influencing the emission of vapor and particulate phase components from diesel engines. In: Ishinishi, N., Koizumi, A., McClellan, R.O. and Stöber, W. (eds), Carcinogenic and mutagenic effects of diesel engine exhaust. Elsevier, Amsterdam, pp 41–64.Google Scholar
  36. 36.
    Möller, L. and Gustafsson, J-Å. (1986). Liquid chromatographic mass spectrometric analysis of 2-nitrofluorene and its derivatives. Biomed. Mass. Spectrom. 13, 681–688.Google Scholar
  37. 37.
    Möller, L., Rafter, J. and Gustafsson, J-Å. (1987). Metabolism of the carcinogenic air pollutant 2-nitrofluorene in the rat. Carcinogenesis, 8, 637–645.CrossRefPubMedGoogle Scholar
  38. 38.
    Möller, L., Törnquist, S., Beije, B., Rafter, J., Toftgård, R. and Gustafsson, J- Å. (1987). Metabolism of the carcinogenic air pollutant 2-nitrofluorene in the isolated rat lung and liver. Carcinogenesis, 8, 1847–1852.CrossRefPubMedGoogle Scholar
  39. 39.
    Möller, L., Corrie, M., Midtvedt, T., Rafter, J. and Gustafsson, J- Å. (1988). The role of the intestinal microflora in the formation of mutagenic metabolites from the carcinogenic air pollutant 2-nitrofluorene. Carcinogenesis, 9, 823–830.CrossRefPubMedGoogle Scholar
  40. 40.
    Törnquist, S., Möller, L., Gabrielsson, J., Gustafsson, J- Å. and Toftgård, R (1989). 2-Nitrofluorene metabolism in the rat lung. Pharmacokinetic and metabolic effects of betanapthoflavone treatment. Carcinogenesis, submitted.Google Scholar
  41. 41.
    Törnquist, S., Sundin, M., Möller, L., Gustafsson, J- Å. and Toftgård, R (1988). Age dependent expression of cytochrome P-450 b and metabolism of the potent carcinogen 2-nitrofluorene in the rat lung. Carcinogenesis, 9, 2209–2214.CrossRefPubMedGoogle Scholar
  42. 42.
    Beije, B. and Möller, L. (1986). Unscheduled DNA-synthesis in the liver and mutagenic activity in the urine of rats exposed to 2-nitrofluorene or 2-acetylaminofluorene. Environ. Mut. 8,10.Google Scholar
  43. 43.
    Beije, B. and Möller, L. (1988). Correlation between induction of unscheduled DNA synthesis in the liver and excretion of mutagenic metabolites in the urine of rats exposed to the carcinogenic air pollutant 2-nitrofluorene. Carcinogenesis, 9, 8, 1465–1470, 1988.CrossRefPubMedGoogle Scholar
  44. 44.
    Möller, L., Torndal, U-B., Gustafsson, J- Å. and Erlksson, L.C. (1989). The air pollutant 2-nitrofluorene as initiator and promotor in a liver model for studies on chemical carcinogenesis. Carcinogenesis, 10,13,435–440.CrossRefPubMedGoogle Scholar
  45. 45.
    Möller, L., Lax, I., and Eriksson, L.C. (1989). Risk assessment of nitrated polycyclic aromatic hydrocarbons via the carcinogenic air pollutant and model substance, 2-nitrofluorene, by two different methods. Carcinogenesis, submitted.Google Scholar
  46. 46.
    Rosenkranz, H.S. and Mermelstein, R. (1983). Mutageniclty and genotoxicity of nitroarenes. All nitro-containing chemicals were not created equal. Mutat. Res. 114, 217.CrossRefPubMedGoogle Scholar
  47. 47.
    Wilson, R.H., DeEds, F. and Cox, A.J. (1941). The toxicity and carcinogenic activity of 2-acetylaminofluorene. Cancer Res., 1, 595.Google Scholar
  48. 48.
    Campbell, R.M. and Lee, M.L. (1984). Capillary column gas chromatographic determination of nitro polycyclic aromatic compounds in particulate extracts. Anal. Chem., 56, 1026.CrossRefGoogle Scholar
  49. 49.
    Bertilsson, T. and Egebäck, (1984). Swedish EPA-report, SNV PM 1739, p 19.Google Scholar
  50. 50.
    Lindner, R.E., Hess, R.A. and Strader, L.F. (1986). Testicular toxicity and infertility in male rats treated with 1,3-dinitrobenzene. J. Toxicol. Environ. Health, 19, 477.CrossRefGoogle Scholar
  51. 51.
    Schuetzle, and Perez, J.M. (1983). Factors influencing the emissions of nitrated-polynuclear aromatic hydrocarbons (nitro-PAH) from diesel engines. J.Air Poll. Control Ass., 33, 751.CrossRefGoogle Scholar
  52. 52.
    Bond, J.A., Medinsky, MA and Dutcher, J.S. (1984). Metabolism of 1-[14C] nitropyrene in isolated perfused rat livers.Toxicol. Appl. Pharmalcol., 75, 531.CrossRefGoogle Scholar
  53. 53.
    Kinouchi, T., Morotomi, M., Mutai, M., Fifer, E.K., Beland, FA and Ohnishi, Y. (1986). Metabolism of 1-nitropyrene in germ-free and conventional rats. Japan J. Cancer Res. (Gann), 77,356.Google Scholar
  54. 54.
    Weisburger, E.K. (1979). N-substituted aryl compounds in carcinogenesis and mutagenesis. National Cancer Institute Monograph, No. 58, p 1.Google Scholar
  55. 55.
    McCann, J., Choi, E., Yamasaki, E. and Ames, B. (1975). Detection of carcinogens as mutagens in the salmonells/microsome test: Assay of 300 chemicals. Proc. Nati. Acad. Sci., 72, 5135.CrossRefGoogle Scholar
  56. 56.
    Morris, H.P., Dubnik, C.S. and Johnson, J.M. (1950). Studies of the carcinogenic action in the rat okf 2-nitro, 2-amino, 2-acetylamino, and 2-diacetylaminofluorene after ingestion and after painting. J.Natl.Cancer inst..10, 1201.PubMedGoogle Scholar
  57. 57.
    Belisario, MA, Carrano, L., DeGlulio, A., Pecce, R. and Buonocore, V. (1987). Effect of liver enzyme inducers on metabolite excretion in rats treated with 1-nitropyrene. Toxicol. Lett., 36, 233.CrossRefPubMedGoogle Scholar
  58. 58.
    Malejka-Giganti, D., Magat, W.J., Adelmann, A.M. and Decker, RW. (1987). Metabolite profile in milk of lactating rats after treatment with a carcinogen, N-2-fluorenylacetamide. Drug Metab. Dispos., 15, 760.PubMedGoogle Scholar
  59. 59.
    Djuric, Z., Fifer, E.K., Howard, P.C. and Beland, F.A. (1986). Oxidative microsomal metabolism of 1-nitropyrene and DNA-binding of oxidized metabolites following nitroreduction. Carcinogenesis, 7, 1073.CrossRefPubMedGoogle Scholar
  60. 60.
    Beland, F.A., Heflich, R.H., Howard, P.C. and Fu, P.P. (1985). In Polycyclic Hydrocarbons and Carcinogenesis, Harvey, R.G., ed. American Chemical Society, Washington D.C., 371.CrossRefGoogle Scholar
  61. 61.
    Cerniglia, C.E., Howard, P.C., Fu, P.P. and Franklin, W. (1984). Metabolism of nitropolycyclic aromatic hydrocarbons by human intestinal microflora. Biochem. Biophys. Res. Commun.,123, 262.CrossRefGoogle Scholar
  62. 62.
    Howard, P.C., Beland, F.A. and Cerniglia, C.E. (1983). Carcinogenesis, 4, 985.CrossRefPubMedGoogle Scholar
  63. 63.
    El Bayoumy, K, Sharma, C., Louis, Y.M., Reddy, B. and Hecht S.S. (1983). The role of intestinal microflora in the metabolic reduction of 1-nitropyrene to 1-aminopyrene in conventional and germfree rats and in humans. Cancer Lett., 19, 311.CrossRefPubMedGoogle Scholar
  64. 64.
    . Harries, G.C., Boobis, A.R, Sesardic, D., Edwards, RJ. and Davies D.S. (1986). Food Chem. Toxicol., 24, 757.CrossRefGoogle Scholar
  65. 65.
    Eddy, E.P., Howard, P.C., McCoy, G.D. and Rosenkranz, H.S. (1987). Mutagenicity, unscheduled DNA synthesis, and metabolism of 1-nitropyrene in the human hepatoma cell line HepG2. Cancer Res., 47, 3163.PubMedGoogle Scholar
  66. 66.
    Boobis, A.R., Brodie, M.J., McManus, M.E., Staiano, N., Thorgeirsson, S.S. and Davies, D.S. (1981). Metabolism and mutagenic activation of 2-acetylaminofluorene by human liver and lung. Adv. Exp. Med. Biol., 136, 1193.PubMedGoogle Scholar
  67. 67.
    McManus, M.E., Trainor, K.J., Morley, AA., Burgess, W., Stupans, I. and Birkett, D.J. (1987). Metabolism of 2-acetylaminofluorene in cultured human lymphocytes. Chem. Pathol. Pharmacol., 55, 409.Google Scholar
  68. 68.
    Moore, B.P., Hicks, RM., Knowles, MA. and Redgraves, S. (1982). Metabolism and binding of benzo(a)pyrene and 2-acetylaminofluor§Öne by short-term organ cultures of human and rat bladder. Cancer Res., 42, 642.PubMedGoogle Scholar
  69. 69.
    Weisburger, J.H., Grantham, P.H., van Horn, E., Steigbigel, N.H., Rall, D.P. and Weisburger, E.K. (1964). Activation and detoxification of N-2-fluoreneylacetamide in man. Cancer Res., 24, 475.PubMedGoogle Scholar
  70. 70.
    Gorbach, S.L. (1982). The intestinal microflora and its colon cancer connection. Infection, 10, 379.CrossRefPubMedGoogle Scholar
  71. 71.
    Dybing, E., Dahl, J.E., Beland, F.A. and Thorgeirsson, S.S. (1986). Cell Biol. Toxicol., 2, 341.CrossRefPubMedGoogle Scholar
  72. 72.
    Bond, JA, Mauderly, J.L. and McClellan, RO. (1984). In: Polynuclear Aromatic Hydrocarbons, Proceedings of the Ninth International on Polynuclear Aromatic Hydrocarbons Symposium, Cooke, M., Dennis, A.J., eds., Batelle Press, Columbus, p 79.Google Scholar
  73. 73.
    Morlske, H-J., Block, I. and Rüden. (1984). Ûber polare organische Verbindungen im Stadtaerosol and deren mutagene Wirksamkeit im Salmonella typhimurlum-Test nach Ames.Forum Stãdte Hygiene, 35, 113.Google Scholar
  74. 74.
    Iida, Y., Daishima, S., Furuya, K., Kikushi, T., Matsushita, H., Tanebe, K., Wu, J., Wan, A-P. and Huang Y-C. (1985). Present state of air pollution in Beijing. Sekei J. Asian Pacific Studies, 111.Google Scholar
  75. 75.
    Ehrenberg, L., personal communication Dep. of Radiation Biology, Univ. of Stockholm, Sweden.Google Scholar
  76. 76.
    Harris, C., Namkung, M.J. and Juchau, M.R. (1987). Regulation of intracellular glutathione in rat embryos and visceral yolk sacs and its effect on 2-nitrofluorene-induced malformations in the whole embryo culture system. Toxicol. Appl. Pharmacol., 88, 141.CrossRefPubMedGoogle Scholar
  77. 77.
    Howard, P.C., Demarco, G.J., Consolo, M.C. and McCoy, G.D. (1987). Differing effects of chronic ethanol consumption by mice on liver microsomal metabolism of xenobiotics: 1-nitropyrene, nicotine, aniline, and n-nitrosopyrrolidine. Mol. Toxicol., 1, 177.PubMedGoogle Scholar
  78. 78.
    Ioannides, C. and Steele, C.M. (1986). Hepatic microsomal mixed-function oxidases by aromatic amines and its relationship to their bioactivation to mutagen. Chem.-Biol. Interact., 59, 129.CrossRefPubMedGoogle Scholar
  79. 79.
    Roberts, L. (1987). Atomic bomb doses reassessed. Science, 238, 1649.CrossRefPubMedGoogle Scholar
  80. 80.
    Solt, D. and Farber, E. (1976). New Principle for the Analysis of Chemical Carcinogenesis. Nature, 262, 701.CrossRefGoogle Scholar
  81. 81.
    Lew, K.K., Nichols, D.G. and Kolbert, A.W. (1983). Nato Cont. Series, 1, 139.Google Scholar
  82. 82.
    Nachtman, J.P. and Wolff, S. (1982). Activity of nitro-polynuclear aromatic hydrocarbons in the sister chromatid exchange assay with and without metabolic activation. Environ. Mut., 4, 1.CrossRefGoogle Scholar
  83. 83.
    McCoy, E. (1984). Role of metabolism on the mutageniclty of nitroareas. In: Biochemical Basis of Chemical Carcinogenesis, Eds., Greim, H, Jung, R., Kramer, M., Marquardt, H. and Oesch, F., Raven Press, New York.Google Scholar
  84. 84.
    Massaro, M., McCartney, M., Rosenkranz, E.J., Anders, M., McCoy, E., Mermelstein, R. and Rosenkranz, H.S. (1983). Evidence that nitroarene metabolites form mutagenic adducts with DNA-adenine as well as with DNA-guanine. Mutat. Res., 122, 243.CrossRefPubMedGoogle Scholar
  85. 85.
    Amacher, D.E., Paillet, S.C., Turner, G.N. (1979). Utility of the mouse lymphoma L5 178Y/TK assay for the detection of chemical mutagens. In: Mammalian Cell Mutagenesis, Banbury Report No. 2, 277.Google Scholar
  86. 86.
    Suzuki, Y. (1985). Studies on development of the sensitive micronucleus test. Part 2 The in vitro method using cultured bone marrow cells.Tokyo Jikeikai Med. J., 100, 707.Google Scholar
  87. 87.
    Saldtanl, T. and Suzuki, Y. (1986). Part 2 Mutagenic activities of air pollutants observed by micronucleus test.Tokyo Jikeikal Med. J., 101, 259.Google Scholar
  88. 88.
    Ohe, T. (1985). Studies on comparative decomposition rate by rat liver homogenate and on micromucleus test of nitrated polycyclic aromatic hydrocarbons. Bull. Environ. Contam. Toxicol., 34, 715.CrossRefPubMedGoogle Scholar
  89. 89.
    Rosenkranz, H.S., McCoy, E.C., Frierson, M. and Klopman, G. (1985). The role of DNA sequence and structure of the electrophile on the mutagenicity of nitroarenes and arylamine derivatives. Environ. Mut. 7, 645.CrossRefGoogle Scholar
  90. 90.
    Andrews, L.S., Pohl, L.R., Hinson, JA. and Gilette, J.R. (1979). Mutagenesis of 2- nitrofluorene (NF), 2-nitrosofluorene (NOF) and 2-hydroxylaminofluorene (NHOHF) for salmonella TA 100 and TA 200 FRToxicol. App’. Pharmacol. 48, A48.Google Scholar
  91. 91.
    Baneljee, T.S., Bhaumik, G., Yu, C-L., Swaminathan, B., Girl, AK., Srivastava, S. and Bhattacharjee, S.B. (1984). Evaluation of the genetoxicity of lac dye. Fd. Chem. Toxicol. 22, 677.CrossRefGoogle Scholar
  92. 92.
    Doudney, C.O., Franke, MA., and Rinaldi, C.N. (1981). The DNA damage activity (DDA) assay and its application to river waters and diesel exhausts. Environ. Internat., 5, 293.CrossRefGoogle Scholar
  93. 93.
    Wangenhelm, J. and Bolcsfoldi, G. (1986). Mouse lymphoma TK+/- assay of 30 compounds. Environ. Mut. 8, 90.Google Scholar
  94. 94.
    Moon, R.C., Rao, K.V.N. and Detrisac, C.J. (1988). Potential carcinogenicity of 1-nitropyrene. In:The fifth Health Effects Institute Annual Conference, Colorado Springs, Health Effects Institute, 15.Google Scholar
  95. 95.
    Simmon, V.F., Rosenkranz, H.S., Zeiger, E., Poirier, L.A. (1979). Mutagenic activity of chemical carcinogens and related compounds in the intraperitoneal host-mediated assay. J.Natl.Cancer inst.,62,911.PubMedGoogle Scholar
  96. 96.
    Littlefield, N.A., Farmer, J.H., Gaylor, D.W. and Sheldon, W.G. (1979). Effects of dose and time in a long-term, low-dose carcinogenic study. J. Environ. Pathol. Toxicol., 3, 17–34.Google Scholar
  97. 97.
    ICRP, no. 26 (1977). Recommendations of the international commission on radiological protection. Pergamon Press, Oxford, vol. 1.Google Scholar

Copyright information

© Springer Science+Business Media New York 1990

Authors and Affiliations

  • L. Möller
    • 1
    • 2
  • J. Rafter
    • 1
    • 2
  • S. Törnquist
    • 1
    • 2
  • L. Eriksson
    • 1
    • 2
  • B. Beije
    • 1
    • 2
  • R. Toftgård
    • 1
    • 2
  • T. Midvedt
    • 1
    • 2
  • M. Corrie
    • 1
    • 2
  • J-Å Gustafsson
    • 1
    • 2
  1. 1.Departments of Medical Nutrition, Medical Microbial Ecology and PathologyKarolinska InstituteStockholmSweden
  2. 2.Department of Genetic and Cellular ToxicologyUniversity of StockholmStockholmSweden

Personalised recommendations