Effective use of the Pig-a gene mutation assay for mutagenicity screening : measuring CD59-deficient red blood cells in rats treated with genotoxic chemicals
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- Kimoto Takafumi
- TEIJIN Pharma Limited
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- Chikura Satsuki
- TEIJIN Pharma Limited
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- Suzuki-Okada Kumiko
- TEIJIN Pharma Limited
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- Kobayashi Xiao-mei
- TEIJIN Pharma Limited
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- Itano Yasuhiro
- TEIJIN Pharma Limited
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- Miura Daishiro
- TEIJIN Pharma Limited
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- Kasahara Yoshinori
- TEIJIN Pharma Limited
書誌事項
- タイトル別名
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- Effective use of the <i>Pig-a</i> gene mutation assay for mutagenicity screening: measuring CD59-deficient red blood cells in rats treated with genotoxic chemicals
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抄録
The Pig-a gene mutation assay using perpherial blood erythrocytes is being investigated as a screening tool for assessing mutagenicity in vivo. In this study, we evaluated two distinct approaches for performing the Pig-a assay in rats. We used antibodies to CD45 or the erythroid marker HIS49 to identify red blood cells (RBCs), and then monitored the kinetics of Pig-a mutant frequency, as measured by the frequency of CD59-deficient RBCs, in rats treated with the genotoxic chemicals, N-ethyl-N-nitrosourea, cyclophosphamide, 4-nitroquinoline-1-oxide, and ethylmethanesulfonate. In some instances, micronucleus frequency also was measured in the same animals. Time- and dose-related increases in Pig-a mutant frequency were found in all the chemical-treated groups, except for the groups treated with cyclophosphamide, which was a potent inducer of micronuclei. The two different approaches we employed were comparable for measuring induced mutant frequencies, but our historical data showed that the mean background frequencies for the CD45/CD59 method and the HIS49/CD59 method were 12.7 × 10-6 and 5.5 ×10-6, respectively. The relatively low, stable background mutant frequency associated with the HIS49/CD59 method indicates that it may have greater power for discriminating weak induced responses. These results suggest that the HIS49/CD59 method is a promising tool for measuring Pig-a mutant RBCs. In addition, differences in their manifestation kinetics and in their relative sensitivity for detecting different test compounds suggest that the combination of the Pig-a assay and the micronucleus assay may be effective in identifying in vivo genotoxicity.
収録刊行物
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- The Journal of Toxicological Sciences
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The Journal of Toxicological Sciences 37 (5), 943-955, 2012
一般社団法人 日本毒性学会
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詳細情報 詳細情報について
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- CRID
- 1390001204905677312
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- NII論文ID
- 130004447007
- 10030876354
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- NII書誌ID
- AN00002808
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- COI
- 1:STN:280:DC%2BC3s%2Fis1OnsQ%3D%3D
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- ISSN
- 18803989
- 03881350
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- NDL書誌ID
- 024030308
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- PubMed
- 23038003
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
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- 抄録ライセンスフラグ
- 使用不可