DNA adduct formation and oxidative stress from the carcinogenic urban air pollutant 3-nitrobenzanthrone and its isomer 2-nitrobenzanthrone, in vitro and in vivo.

2.50
Hdl Handle:
http://hdl.handle.net/10146/27992
Title:
DNA adduct formation and oxidative stress from the carcinogenic urban air pollutant 3-nitrobenzanthrone and its isomer 2-nitrobenzanthrone, in vitro and in vivo.
Authors:
Nagy, Eszter; Adachi, Shuichi; Takamura-Enya, Takeji; Zeisig, Magnus; Moller, Lennart
Abstract:
The carcinogenic vehicle emission product 3-nitrobenzanthrone (3-NBA) is known to rearrange in the atmosphere to the isomer 2-nitrobenzanthrone (2-NBA), which exists in 70-fold higher concentration in ambient air. The genotoxicity of 2-NBA and 3-NBA was studied both in vitro (human cell lines A549 and HepG2) and in vivo (F344 female rats intra-tracheally administered 5 mg/kg body weight of 3-NBA) models, using the (32)P-HPLC and the single-cell gel electrophoresis (Comet assay) methods. In vitro, also the parent compound benzanthrone (BA) and the metabolite 3-aminobenzanthrone (3-ABA) were evaluated. 3-NBA gave highest levels of DNA adducts in the two cell lines, but significantly higher in HepG2 (relative adduct level approximately 500 adducts/10(8) normal nucleotides), whereas 2-NBA formed about one-third and one-twentieth of the DNA adduct amount in A549 and HepG2 cells, respectively. 3-ABA formed only minute amounts of DNA adducts and only in the A549 cells, whereas BA did not give rise to any detectable levels. The DNA adduct patterns from 3-NBA were similar between the two model systems, but differed somewhat for 2-NBA. The oxidative stress induced by BA was almost as high as what was observed for 3-NBA and 3-ABA in both cell lines, and 2-NBA induced lowest level of oxidative stress. The oxidative stress and DNA adduct level, in whole blood, was significantly increased by 3-NBA but not by 2-NBA. However, 2-NBA showed similar toxicity to 3-NBA, with respect to DNA adduct formation in vivo, hence it is important to further study 2-NBA as a potential contributor to health risk. While DNA adduct level in the 3-NBA-exposed animals reached a peak around 1 and 2 days after instillation, 2-NBA-treated animals showed a tendency towards a continuing increase at the end of the study.
Citation:
Mutagenesis 2007, 22 (2):135-145
Journal:
Mutagenesis
Issue Date:
Mar-2007
URI:
http://hdl.handle.net/10146/27992
DOI:
10.1093/mutage/gel067
PubMed ID:
17267818
Additional Links:
http://mutage.oxfordjournals.org/cgi/content/full/22/2/135#BIBL
Type:
Article
Language:
en
ISSN:
0267-8357
Sponsors:
This study was supported by the Swedish Environmental Protection Agency and Global Environment Protection from Ministry of the Environment, Japan. This work was partly supported by ECNIS (Environmental Cancer Risk, Nutrition and Individual Susceptibility), a network of excellence operating within the European Union 6th Framework Programme, Priority 5: "Food, Quality and Safety" (Contract No. 513943).
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Articles

Full metadata record

DC FieldValue Language
dc.contributor.authorNagy, Eszter-
dc.contributor.authorAdachi, Shuichi-
dc.contributor.authorTakamura-Enya, Takeji-
dc.contributor.authorZeisig, Magnus-
dc.contributor.authorMoller, Lennart-
dc.date.accessioned2008-05-26T06:59:22Z-
dc.date.available2008-05-26T06:59:22Z-
dc.date.issued2007-03-
dc.identifier.citationMutagenesis 2007, 22 (2):135-145en
dc.identifier.issn0267-8357-
dc.identifier.pmid17267818-
dc.identifier.doi10.1093/mutage/gel067-
dc.identifier.urihttp://hdl.handle.net/10146/27992-
dc.description.abstractThe carcinogenic vehicle emission product 3-nitrobenzanthrone (3-NBA) is known to rearrange in the atmosphere to the isomer 2-nitrobenzanthrone (2-NBA), which exists in 70-fold higher concentration in ambient air. The genotoxicity of 2-NBA and 3-NBA was studied both in vitro (human cell lines A549 and HepG2) and in vivo (F344 female rats intra-tracheally administered 5 mg/kg body weight of 3-NBA) models, using the (32)P-HPLC and the single-cell gel electrophoresis (Comet assay) methods. In vitro, also the parent compound benzanthrone (BA) and the metabolite 3-aminobenzanthrone (3-ABA) were evaluated. 3-NBA gave highest levels of DNA adducts in the two cell lines, but significantly higher in HepG2 (relative adduct level approximately 500 adducts/10(8) normal nucleotides), whereas 2-NBA formed about one-third and one-twentieth of the DNA adduct amount in A549 and HepG2 cells, respectively. 3-ABA formed only minute amounts of DNA adducts and only in the A549 cells, whereas BA did not give rise to any detectable levels. The DNA adduct patterns from 3-NBA were similar between the two model systems, but differed somewhat for 2-NBA. The oxidative stress induced by BA was almost as high as what was observed for 3-NBA and 3-ABA in both cell lines, and 2-NBA induced lowest level of oxidative stress. The oxidative stress and DNA adduct level, in whole blood, was significantly increased by 3-NBA but not by 2-NBA. However, 2-NBA showed similar toxicity to 3-NBA, with respect to DNA adduct formation in vivo, hence it is important to further study 2-NBA as a potential contributor to health risk. While DNA adduct level in the 3-NBA-exposed animals reached a peak around 1 and 2 days after instillation, 2-NBA-treated animals showed a tendency towards a continuing increase at the end of the study.en
dc.description.sponsorshipThis study was supported by the Swedish Environmental Protection Agency and Global Environment Protection from Ministry of the Environment, Japan. This work was partly supported by ECNIS (Environmental Cancer Risk, Nutrition and Individual Susceptibility), a network of excellence operating within the European Union 6th Framework Programme, Priority 5: "Food, Quality and Safety" (Contract No. 513943).-
dc.language.isoenen
dc.relation.urlhttp://mutage.oxfordjournals.org/cgi/content/full/22/2/135#BIBL-
dc.subject.meshAir Pollutants-
dc.subject.meshAnimals-
dc.subject.meshBenz(a)Anthracenes-
dc.subject.meshCarcinogens-
dc.subject.meshCell Line-
dc.subject.meshChromatography, High Pressure Liquid-
dc.subject.meshDNA Adducts-
dc.subject.meshFemale-
dc.subject.meshHumans-
dc.subject.meshIsomerism-
dc.subject.meshOxidative Stress-
dc.subject.meshRats-
dc.subject.meshRats, Inbred F344-
dc.subject.meshTime Factors-
dc.titleDNA adduct formation and oxidative stress from the carcinogenic urban air pollutant 3-nitrobenzanthrone and its isomer 2-nitrobenzanthrone, in vitro and in vivo.en
dc.typeArticleen
dc.identifier.journalMutagenesisen
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