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Nitroarenes pp 157-166 | Cite as

Comparison of the Mutagenic Potency of DNA Adducts Formed by Reactive Derivatives of Aflatoxin, Benzidine and 1-Nitropyrene in a Plasmid System

  • Carl N. Martin
  • Gary S. Jennings
Part of the Environmental Science Research book series (ESRH, volume 40)

Abstract

1-Nitropyrene is an ubiquitous environmental pollutant which has been detected in the urban atmosphere in many areas of the world (1). It is generated primarily by incomplete combustion of fossil fuels and thus is present in relatively high concentrations in emissions such as diesel engine exhaust fumes (2, 3) and power station fly-ash (4, 5). This compound has been shown to be biologically active in a number of in vitro genotoxicity assay systems, inducing mutation in Salmonella typhimurium (6) and inducing mutations, unscheduled DNA synthesis, transformation or chromosomal rearrangements in a variety of mammalian cell lines (7–10). 1-nitropyrene has also been shown to be carcinogenic in laboratory animals (11, 12). The activation of 1-nitropyrene has been shown to involve a sequential two-electron reduction leading to the formation of 1-NOP, N-OH-l-aminopyrene and 1-aminopyrene (13, 14). The N-hydroxy derivative has been shown to be an ultimate DNA-reactive species (13). The adduct produced in DNA by the reactive metabolite of 1-nitropyrene has been identified in bacterial systems (15) and in rat liver (16) as N-(deoxyguanosin-8-yl)-1-aminopyrene. Thus, 1-nitropyrene is a compound to which the human population is exposed and is biologically active in a number of experimental systems. However, very little information is available as to the relative carcinogenic risk to humans chronically exposed to this compound.

Keywords

Plasmid System Diesel Engine Exhaust Caesium Chloride Mutagenic Potency Mouse Lymphoma L1578Y 
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.

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References

  1. 1.
    Gibson T, (1982) Nitroderives of polynuclear aromatic hydrocarbons in airborne and source particulate. Atmos. Environ. 16, 2037–2040.CrossRefGoogle Scholar
  2. 2.
    Pederson T and Siak J S (1981) The role of nitroaromatic compounds in the direct-acting mutagenicity of diesel particle extracts. J. Appl. Toxicol. 1, 54–60.CrossRefPubMedGoogle Scholar
  3. 3.
    Salmeen I, Durisin A M, Prater T J, Riley T; and Schuetzle D (1982) Contribution of 1-nitropyrene to direct-acting Ames assay mutagenicities of diesel particulate extracts. Mutat. Res. 104, 17–23.CrossRefPubMedGoogle Scholar
  4. 4.
    Wei C, Raobe O G and Rosenblatt L S (1982) Microbial detection of mutagenic nitro-organic compounds in filtrates of coal fly ash. Environ. Mutagenesis 4, 249–258.CrossRefGoogle Scholar
  5. 5.
    Li A P, Clark C R, Hanson R L, Henderson T R and Hobbs C H (1982) Coal combustion fly ash extract as direct-acting mutagen in Salmonella and promutagen in Chinese hamster ovary cells. Environ. Mutagenesis 3, 407–408.Google Scholar
  6. 6.
    Mermelstein R, Kiriazides, D K, Butler M, McCoy E C and Rosenkranz H S (1981) The extraordinary mutagenicity of nitropyrenes in bacteria. Mutat. Res 89, 187–196.CrossRefPubMedGoogle Scholar
  7. 7.
    Nakayasu M, Sakamoto H, Wakabayashi K, Terada M, Sugimura T and Rosenkranz H S (1982) Potent mutagenic activity of nitropyrenes on Chinese hamster lung cells with diphtheria toxin resistance as a selective marker. Carcinogenesis 3, 917–922.CrossRefPubMedGoogle Scholar
  8. 8.
    Li A P and Dutcher J S (1983) Mutagenicity of mono-, di- and trinitropyrenes in Chimese hamster ovary cells. Mutat. Res. Lett. 119, 387–392.CrossRefGoogle Scholar
  9. 9.
    Kawachi T (1982) Mutagenicity and carcinogenicity of nitropyrene. In: Rickert D (ed), The Toxicity of Nitroaromatic Compounds. Hemisphere, New York.Google Scholar
  10. 10.
    Natchman J P and Wolff S (1982) Activity of nitropolynuclear aromatic hydrocarbons in the sister chromatid exchange assay with and without metabolic activation. Environ. Mutageneses 4, 1–5.CrossRefGoogle Scholar
  11. 11.
    Hirose M, Lee M S, Wang C Y and King C M (1984) Induction of rat mammary gland tumours by 1-nitropyrene, a recently recognised environmental mutagen. Cancer Res. 44, 1158–1162.PubMedGoogle Scholar
  12. 12.
    El-Bayoumi K, Hecht S S, Sackl T and Stoner G D (1984) Tumorigenicity and metabolism of 1-nitropyrene in A/J mice. Carcinogenesis 5, 1499–1452.CrossRefGoogle Scholar
  13. 13.
    Heflich R H, Howard P C and Beland F A (1985) 1-Nitrocopyrene: an intermediate in the metabolic activation of 1-nitropyrene to a mutagen in Salmonella typhimurium TA1538. Mutat. Res. 149, 25–32.CrossRefPubMedGoogle Scholar
  14. 14.
    Beland F A, Ribovich M, Howard P C, Heflich R H, Kurian P and Milo G E (1986) Cytotoxicity, cellular tranformation and DNA adducts in normal human diploid fibroblats exposed to 1-nitropyrene, a reduced derivative of the environmental contaminant, 1-nitropyrene. Carcinogenesis 7, 1279–1283.CrossRefPubMedGoogle Scholar
  15. 15.
    Howard P C, Heflich R H, Evans F E and Beland F A (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
  16. 16.
    Stanton C A, Chow F L, Phillips D H, Grover P L, Garner R C and Martin C N (1985) Evidence of N-(deoxyguanosin-8-yl)-1-aminopyrene as a major DNA adduct in female rats treated with 1-nitropyrene. Carcinogenesis 6, 535–538.CrossRefPubMedGoogle Scholar
  17. 17.
    Martin C N and Garner R C (1977) Aflatoxin B-oxide generated by chemical or enzymic oxidation of aflatoxin B1 causes guanine substitution in nucleic acids. Nature 267, 863–865.CrossRefPubMedGoogle Scholar
  18. 18.
    Essigmann J M, Croy R G, Nadyan A M, Busby W F, Reinhold V N, Buchi G and Wogan G N (1977) Structural identification of the major DNA adduct formed by aflatoxin B1 in vitro. Proc. Natl. Acad. Sci. 74, 1870–1874.CrossRefPubMedGoogle Scholar
  19. 19.
    Martin C N, Beland, F A, Roth, R W and Kadlubar, F F (1982) Covalent binding of benzidine and N-acetylbenzidine to DNA at the C-8 atom of deoxyguanosine in vivo and in vitro. Cancer Res. 42, 2678–2686.PubMedGoogle Scholar
  20. 20.
    Swenson D H, Miller J A and Miller E C (1975) The reactivity and carcinogenicity of aflatoxin B1-2, 3-dichloride, a model for the putative 2, 3-oxide metabolite of aflatoxin B1. Cancer Res. 35, 3811–3823PubMedGoogle Scholar
  21. 21.
    Mizusawa H, Lee C-H and Kakefuda T (1981) Alteration of plasmid DNA-mediated transformation and mutation induced by covalent binding of benzo(a)pyrene-7, 8-dihydrodiol-9, 10, -epoxide in Escherichia coli. Mutation Res. 82, 47–57.CrossRefPubMedGoogle Scholar
  22. 22.
    McCoy E C, Anders M, McCartney M, Howard P C, Beland F A and Rosenkranz H S (1984). The recombinogenic inactivity of 1-nitropyrene for yeast is due to a deficiency in a functional nitroreductase. Mutation Res. 139, 115–118.CrossRefPubMedGoogle Scholar
  23. 23.
    Stanton C A, Garner RC, and Martin C N (1988). The mutagenicity and DNA base sequence changes induced by 1-nitroso-and 1-nitropyrene in the -cI gene of lambda prophage. Carcinogenesis 9, 1153–1157.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1990

Authors and Affiliations

  • Carl N. Martin
    • 1
  • Gary S. Jennings
    • 1
  1. 1.Cancer Research UnitUniversity of YorkYorkEngland

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