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In vivo metabolism and genotoxic effects of nitrated polycyclic aromatic hydrocarbons.

During incomplete combustion of organic matter, nitro-polycyclic aromatic hydrocarbons (nitro-PAHs), are formed in a reaction that is catalyzed by a low pH. 2-Nitrofluorene (NF), a marker for nitro-PAHs, is metabolized in vivo by two different routes. After inhalation, potent mutagenic metabolites,...

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Autor principal: Möller, L
Formato: Texto
Lenguaje:English
Publicado: 1994
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1566915/
https://www.ncbi.nlm.nih.gov/pubmed/7821288
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author Möller, L
author_facet Möller, L
author_sort Möller, L
collection PubMed
description During incomplete combustion of organic matter, nitro-polycyclic aromatic hydrocarbons (nitro-PAHs), are formed in a reaction that is catalyzed by a low pH. 2-Nitrofluorene (NF), a marker for nitro-PAHs, is metabolized in vivo by two different routes. After inhalation, potent mutagenic metabolites, hydroxylated nitrofluorenes (OH-NFs), are formed. The metabolites are distributed by systemic circulation. After oral administration, NF is reduced to the corresponding amine, a reaction mediated by the intestinal microflora. This metabolite is acetylated to 2-acetylaminofluorene (AAF), a potent carcinogen. Further ring-hydroxylation of AAF leads to detoxification and excretion. Induction of cytochrome P450s affects the metabolism, and more OH-NFs are formed. As a consequence, more mutagenic metabolites are found in the circulation. OH-NFs are excreted in the bile 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 is a direct-acting mutagen in bacterial assays and an initiator and promoter of the carcinogenic process, and gives rise to DNA adduct formation in laboratory animals.
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spelling pubmed-15669152006-09-19 In vivo metabolism and genotoxic effects of nitrated polycyclic aromatic hydrocarbons. Möller, L Environ Health Perspect Research Article During incomplete combustion of organic matter, nitro-polycyclic aromatic hydrocarbons (nitro-PAHs), are formed in a reaction that is catalyzed by a low pH. 2-Nitrofluorene (NF), a marker for nitro-PAHs, is metabolized in vivo by two different routes. After inhalation, potent mutagenic metabolites, hydroxylated nitrofluorenes (OH-NFs), are formed. The metabolites are distributed by systemic circulation. After oral administration, NF is reduced to the corresponding amine, a reaction mediated by the intestinal microflora. This metabolite is acetylated to 2-acetylaminofluorene (AAF), a potent carcinogen. Further ring-hydroxylation of AAF leads to detoxification and excretion. Induction of cytochrome P450s affects the metabolism, and more OH-NFs are formed. As a consequence, more mutagenic metabolites are found in the circulation. OH-NFs are excreted in the bile 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 is a direct-acting mutagen in bacterial assays and an initiator and promoter of the carcinogenic process, and gives rise to DNA adduct formation in laboratory animals. 1994-10 /pmc/articles/PMC1566915/ /pubmed/7821288 Text en
spellingShingle Research Article
Möller, L
In vivo metabolism and genotoxic effects of nitrated polycyclic aromatic hydrocarbons.
title In vivo metabolism and genotoxic effects of nitrated polycyclic aromatic hydrocarbons.
title_full In vivo metabolism and genotoxic effects of nitrated polycyclic aromatic hydrocarbons.
title_fullStr In vivo metabolism and genotoxic effects of nitrated polycyclic aromatic hydrocarbons.
title_full_unstemmed In vivo metabolism and genotoxic effects of nitrated polycyclic aromatic hydrocarbons.
title_short In vivo metabolism and genotoxic effects of nitrated polycyclic aromatic hydrocarbons.
title_sort in vivo metabolism and genotoxic effects of nitrated polycyclic aromatic hydrocarbons.
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1566915/
https://www.ncbi.nlm.nih.gov/pubmed/7821288
work_keys_str_mv AT mollerl invivometabolismandgenotoxiceffectsofnitratedpolycyclicaromatichydrocarbons