Air pollutants, a possible factor in gastrointestinal cancer

L. Moller, S. Tornquist, R. Toftgard, J. Rafter, T. Midtvedt, Jan-Ake Gustafsson

Research output: Contribution to journalArticle

Abstract

During incomplete combustion of organic matter there is formation of polycyclic aromatic hydrocarbons (PAH), which can react with oxides of nitrogen, with the generation 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 metabolized in vivo 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 ring-hydroxylation of AAF leads to detoxification and excretion. Induction of cytochrome P450c, 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, 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 initiator 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 at a nonneglectable level.

Original languageEnglish (US)
Pages (from-to)57-70
Number of pages14
JournalActa Chirurgica Scandinavica, Supplement
Volume157
Issue number562
StatePublished - Jan 1 1991

ASJC Scopus subject areas

  • Surgery

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