Genotoxicity of styrene-acrylonitrile trimer in brain, liver, and blood cells of weanling F344 rats

被引：10
作者：
Hobbs, Cheryl A. [1 ]
Chhabra, Rajendra S. [2 ]
Recio, Leslie [1 ]
Streicker, Michael [3 ]
Witt, Kristine L. [2 ]
机构：
[1] Dept Genet & Mol Toxicol, Res Triangle Pk, NC USA
[2] NIEHS, Div Natl Toxicol Program, Res Triangle Pk, NC 27709 USA
[3] ILS Inc, Invest Toxicol Div, Res Triangle Pk, NC 27709 USA
来源：
ENVIRONMENTAL AND MOLECULAR MUTAGENESIS | 2012年 / 53卷 / 03期
关键词：
chromosomal damage; DNA damage; Comet assay; micronuclei; superfund; childhood cancer; ZERO DOSE CONTROL; COMET ASSAY; MICRONUCLEUS ASSAY; DNA-DAMAGE; CHEMICALS; FREQUENCY; SENSITIVITY; GUIDELINES; EXPOSURE; MUTANTS;
D O I：
10.1002/em.21680
中图分类号：
X [环境科学、安全科学];
学科分类号：
08 ; 0830 ;
摘要：
Styreneacrylonitrile Trimer (SAN Trimer), a by-product in production of acrylonitrile styrene plastics, was identified at a Superfund site in Dover Township, NJ, where childhood cancer incidence rates were elevated for a period of several years. SAN Trimer was therefore tested by the National Toxicology Program in a 2-year perinatal carcinogenicity study in F344/N rats and a bacterial mutagenicity assay; both studies gave negative results. To further characterize its genotoxicity, SAN Trimer was subsequently evaluated in a combined micronucleus (MN)/Comet assay in juvenile male and female F344 rats. SAN Trimer (37.5, 75, 150, or 300 mg/kg/day) was administered by gavage once daily for 4 days. Micronucleated reticulocyte (MN-RET) frequencies in blood were determined by flow cytometry, and DNA damage in blood, liver, and brain cells was assessed using the Comet assay. Highly significant dose-related increases (P < 0.0001) in MN-RET were measured in both male and female rats administered SAN Trimer. The RET population was reduced in high dose male rats, suggesting chemical-related bone marrow toxicity. Results of the Comet assay showed significant, dose-related increases in DNA damage in brain cells of male (P < 0.0074) and female (P < 0.0001) rats; increased levels of DNA damage were also measured in liver cells and leukocytes of treated rats. Chemical-related cytotoxicity was not indicated in any of the tissues examined for DNA damage. The results of this subacute MN/Comet assay indicate induction of significant genetic damage in multiple tissues of weanling F344 male and female rats after oral exposure to SAN Trimer. Environ. Mol. Mutagen. 2012. (c) 2012 Wiley Periodicals, Inc.
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页码：227 / 238
页数：12
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