Evaluation of a single-dose PIGRET assay for cisplatin in rats compared with the RBC Pig-a assay.
Mutat Res Genet Toxicol Environ Mutagen
; 811: 97-101, 2016 Nov 15.
Article
em En
| MEDLINE
| ID: mdl-27931823
ABSTRACT
As a part of a collaborative study of the Pig-a assay by the Mammalian Mutagenicity Study Group of the Japanese Environmental Mutagen Society, a genotoxicity study on cisplatin was performed using red blood cell (RBC) Pig-a and PIGRET assays. The dose levels were set at 0 (vehicle, physiological saline), 0.5, 1, and 2 mg/kg, and cisplatin was administered intravenously once to male F344 rats. The RBC Pig-a and PIGRET assays were performed using peripheral blood collected at pre-dosing and 1, 2 and 4 weeks after dosing. In the RBC Pig-a assay, an increase in the Pig-a mutant frequency (MF) was observed at week 4 in the high dose group. Although a significant increase in the Pig-a MF was also observed at week 2 in all cisplatin-treated groups, it was considered that this change was caused by a low MF in the vehicle control group and not to be biologically relevant. In the PIGRET assay, the Pig-a MF was increased at weeks 1, 2 and 4 in the high dose group. In addition, the means of the vehicle control group's Pig-a MFs in the PIGRET assay were lower than those in the RBC Pig-a assay. Based on the above results, cisplatin was determined to have mutagenicity under the conditions of this study, and it was demonstrated that the PIGRET assay was an appropriate tool to evaluate the in vivo mutagenicity much earlier than the RBC Pig-a assay.
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Base de dados:
MEDLINE
Assunto principal:
Reticulócitos
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Cisplatino
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Eritrócitos
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Proteínas de Membrana
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Testes de Mutagenicidade
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Mutagênicos
Limite:
Animals
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article