Document Detail


Genotoxicity of 3,6-dinitrobenzo[e]pyrene, a novel mutagen in ambient air and surface soil, in mammalian cells in vitro and in vivo.
MedLine Citation:
PMID:  19273466     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
3,6-Dinitrobenzo[e]pyrene (3,6-DNBeP), newly identified in airborne particles and surface soil, is a potent mutagen in Salmonella typhimurium. The present study investigated the genotoxic potency of 3,6-DNBeP in vitro and in vivo using mammalian cell strains (Chinese hamster CHL/IU and human HepG2) and ICR mice, respectively. In the hprt gene mutation assay using HepG2 cells, the spontaneous mutant frequency was 61.1 per 10(5) clonable cells, which increased to 229 per 10(5) clonable cells after treatment with 1.0 microg/ml (3 microM) 3,6-DNBeP. Notably, in HepG2 cells with increased N-acetyltransferase 2 activity, the mutant frequency increased to 648 per 10(5) clonable cells by treatment of 1.0 microg/ml (3 microM) 3,6-DNBeP. The sister chromatid exchange frequency increased approximately three times the control level in HepG2 cells treated with 3,6-DNBeP at a concentration of 1.0 microg/ml (3 microM). In HepG2 and CHL/IU cells, the frequency of the cells with micronuclei was 0.9 and 1.2%, and the frequencies increased to 2.3 and 7.6% after 1.0 microg/ml (3 microM) 3,6-DNBeP-treatment, respectively. The H2AX phosphorylation level increased 8-fold compared with the background level with 1.0 microg/ml (3 microM) 3,6-DNBeP-treatment in HepG2 cells. Moreover, the comet assay showed that 3,6-DNBeP produced DNA damage in the cells of liver, kidney, lung and bone marrow in ICR mice 3 h after intraperitoneal injection at 40 mg/kg (0.12 mmol/kg) body weight. These data indicate that 3,6-DNBeP is genotoxic to mammalian cells in vitro and in vivo.
Authors:
Masanobu Kawanishi; Tetsushi Watanabe; Soichiro Hagio; Sayaka Ogo; Chiaki Shimohara; Rika Jouchi; Saori Takayama; Tomohiro Hasei; Teruhisa Hirayama; Yoshimitsu Oda; Takashi Yagi
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-03-08
Journal Detail:
Title:  Mutagenesis     Volume:  24     ISSN:  1464-3804     ISO Abbreviation:  Mutagenesis     Publication Date:  2009 May 
Date Detail:
Created Date:  2009-04-30     Completed Date:  2009-06-16     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8707812     Medline TA:  Mutagenesis     Country:  England    
Other Details:
Languages:  eng     Pagination:  279-84     Citation Subset:  IM    
Affiliation:
Environmental Genetics Laboratory, Frontier Science Innovation Center and Graduate School of Science, Osaka Prefecture University, Gakuen-cho Naka-ku, Sakai, Japan.
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MeSH Terms
Descriptor/Qualifier:
Animals
Benzo(a)pyrene / analogs & derivatives*,  chemistry,  toxicity
Cell Line, Tumor
Comet Assay
Cricetinae
Cricetulus
DNA Primers / genetics
Environmental Pollutants / toxicity*
Histones / metabolism
Humans
Mice
Mice, Inbred ICR
Micronucleus Tests
Molecular Structure
Mutation / drug effects*
Phosphorylation / drug effects
Reverse Transcriptase Polymerase Chain Reaction
Sister Chromatid Exchange / drug effects*
Chemical
Reg. No./Substance:
0/DNA Primers; 0/Environmental Pollutants; 0/H2AFX protein, human; 0/Histones; 128714-76-1/3,6-dinitrobenzopyrene; 50-32-8/Benzo(a)pyrene

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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