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)


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.


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

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