TY - JOUR
T1 - Metabolism of the carcinogenic air pollutant 2-nitrofluorene in the isolated perfused rat lung and liver
AU - Möller, L.
AU - Törnquist, S.
AU - Beije, B.
AU - Rafter, J.
AU - Toftgard, R.
AU - Gustafsson, J. Å
N1 - Funding Information:
We wish to thank Christina Thulin, Ingegerd Muhonen, Lars Nybom and Mary Ann Zetterqvist for excellent technical assistance. This project was supported by the National Swedish Environmental Protection Board, the Swedish Cancer Society, the US National Cancer Institute (CA 42054) and the Swedish Tobacco Company.
Copyright:
Copyright 2010 Elsevier B.V., All rights reserved.
PY - 1987/12
Y1 - 1987/12
N2 - The metabolism of 2-nitrofluorene (NF), a model substance for nitrated polycyclic aromatic hydrocarbons, was studied in the isolated perfused rat lung and liver. NF has been identified in urban air and diesel exhaust and occurs in the gas, as well as in the particulate phase. Therefore, it is conceivable that the lung represents one point of entry of this compound into the body. The lung metabolizes NF to hydroxylated NFs, mainly 9-hydroxy-NF, independently of the route of administration, (intravascular or intratracheal). After intratracheal administration, NF is rapidly excreted into the perfusate, indicating that other organs might be exposed to unmetabolized NF. The liver excretes NF metabolites as biliary glucuronides. Untreated bile is not mutagenic. However, after β-glucuronidase treatment of bile, direct-acting mutagens were detected. The mutagenic metabolites in β-glucuronidase-treated bile were the same as identified in the perfusate of the isolated lung. Since β-glucuronidase is an enzyme found in the human intestinal microflora, inhalation of NF could result in the liberation of genotoxic metabolites in the colon.
AB - The metabolism of 2-nitrofluorene (NF), a model substance for nitrated polycyclic aromatic hydrocarbons, was studied in the isolated perfused rat lung and liver. NF has been identified in urban air and diesel exhaust and occurs in the gas, as well as in the particulate phase. Therefore, it is conceivable that the lung represents one point of entry of this compound into the body. The lung metabolizes NF to hydroxylated NFs, mainly 9-hydroxy-NF, independently of the route of administration, (intravascular or intratracheal). After intratracheal administration, NF is rapidly excreted into the perfusate, indicating that other organs might be exposed to unmetabolized NF. The liver excretes NF metabolites as biliary glucuronides. Untreated bile is not mutagenic. However, after β-glucuronidase treatment of bile, direct-acting mutagens were detected. The mutagenic metabolites in β-glucuronidase-treated bile were the same as identified in the perfusate of the isolated lung. Since β-glucuronidase is an enzyme found in the human intestinal microflora, inhalation of NF could result in the liberation of genotoxic metabolites in the colon.
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U2 - 10.1093/carcin/8.12.1847
DO - 10.1093/carcin/8.12.1847
M3 - Article
C2 - 3677309
AN - SCOPUS:0023629865
SN - 0143-3334
VL - 8
SP - 1847
EP - 1852
JO - Carcinogenesis
JF - Carcinogenesis
IS - 12
ER -