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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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Formato: | Texto |
Lenguaje: | English |
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1994
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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. |
format | Text |
id | pubmed-1566915 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 1994 |
record_format | MEDLINE/PubMed |
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 |