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  • 1
    Keywords: CELLS ; IN-VITRO ; CELL ; human ; IN-VIVO ; LUNG ; MODEL ; PATHWAY ; PATHWAYS ; VITRO ; VIVO ; SYSTEM ; liver ; MICE ; TIME ; ACTIVATION ; DNA ; 3-aminobenzanthrone ; 3-nitrobenzanthrone ; AIR ; CARCINOGENESIS ; DIESEL EXHAUST ; DNA ADDUCT FORMATION ; CONTAMINANT 3-NITROBENZANTHRONE ; BINDING ; bone marrow ; BONE-MARROW ; MOUSE ; MUTANT ; TRANSGENIC MICE ; ASSAY ; genetics ; genotoxicity ; DNA-BINDING ; METABOLIC-ACTIVATION ; NUCLEOTIDES ; POLYCYCLIC AROMATIC-HYDROCARBONS ; EPITHELIAL-CELLS ; ADDUCTS ; heredity ; BODIES ; RE ; air pollution ; INCREASE ; ADDUCT FORMATION ; LEVEL ; BONE ; ENGLAND ; PREDICT ; INCREASES ; ENVIRONMENTAL-POLLUTANT 3-NITROBENZANTHRONE ; NOV ; outcome ; MARROW ; NUCLEOTIDE ; CARCINOGEN 3-NITROBENZANTHRONE ; HUMAN METABOLITE ; URBAN AIR-POLLUTION
    Abstract: FE1 lung epithelial cells derived from Muta (TM) Mouse are a new model system to provide in vitro mutagenicity data with the potential to predict the outcome of an in vivo Muta (TM) Mouse test. 3-Nitrobenzanthrone (3-NBA) is a potent mutagen and suspected human carcinogen identified in diesel exhaust and urban air pollution. We investigated the mutagenicity and DNA binding of 3-NBA and its main metabolite 3-aminobenzanthrone (3-ABA) in vitro and in vivo in the Muta (TM) Mouse assay. Mice were treated with 3-NBA or 3-ABA (0, 2 or 5 mg/kg body weight/day) by gavage for 28 days and 28 days later lacZ mutant frequency (MF) was determined in liver, lung and bone marrow. For both compounds, dose-related increases in MF were seen in liver and bone marrow, but not in lung; mutagenic activity was similar to 2-fold lower for 3-ABA than for 3-NBA. With 3-NBA, highest DNA adduct levels (measured by P-32-post-labelling) were found in liver (similar to 230 adducts per 10(8) nucleotides) with levels 20- to 40-fold lower in bone marrow and lung. With 3-ABA, DNA adduct levels were again highest in the liver, but similar to 4-fold lower than for 3-NBA. FE1 cells were exposed to up to 10 mu g/ml 3-NBA or 3-ABA for 6 h with or without exogenous activation (S9) and harvested after 3 days. For 3-NBA, there was a dose-related increase in MF both with and without S9 mix, which was 〉 10 times higher than observed in vivo. At the highest concentration of 3-ABA (10 mu g/ml), we found only around a 2-fold increase in MF relative to controls. DNA adduct formation in FE1 cells was dose-dependent for both compounds, but 10- to 20-fold higher for 3-NBA compared to 3-ABA. Collectively, our data indicate that Muta (TM) Mouse FE1 cells are well suited for cost-effective testing of suspected mutagens with different metabolic activation pathways as a guide for subsequent in vivo Muta (TM) Mouse testing
    Type of Publication: Journal article published
    PubMed ID: 18635558
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  • 2
    ISSN: 1432-1904
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Natural Sciences in General
    Type of Medium: Electronic Resource
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