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Red blood cell Pig-a assay and PIGRET assay in rats with azathioprine.
Yoshida, Ikuma; Matsumoto, Akemi; Sakai, Yumi; Harada, Yumiko; Hashizume, Tsuneo.
Affiliation
  • Yoshida I; Drug Safety Research Laboratories, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, 26-1, Muraoka-Higashi 2-chome, Fujisawa, Kanagawa 251-8555, Japan.
  • Matsumoto A; Drug Safety Research Laboratories, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, 26-1, Muraoka-Higashi 2-chome, Fujisawa, Kanagawa 251-8555, Japan.
  • Sakai Y; Drug Safety Research Laboratories, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, 26-1, Muraoka-Higashi 2-chome, Fujisawa, Kanagawa 251-8555, Japan.
  • Harada Y; Drug Safety Research Laboratories, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, 26-1, Muraoka-Higashi 2-chome, Fujisawa, Kanagawa 251-8555, Japan.
  • Hashizume T; Drug Safety Research Laboratories, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, 26-1, Muraoka-Higashi 2-chome, Fujisawa, Kanagawa 251-8555, Japan. Electronic address: tsuneo.hashizume@takeda.com.
Article in En | MEDLINE | ID: mdl-27931816
A new in vivo gene mutation assay has been developed based on the phosphatidylinositol glycan anchor biosynthesis, Class A gene (Pig-a in rodents) as an endogenous reporter. Using this Pig-a assay, the in vivo mutagenicity of a single dose of azathioprine (Aza) was investigated in red blood cells (RBC Pig-a assay) and reticulocytes (PIGRET) of rats. Eight-week old male rats were orally dosed once with Aza at 50, 100 and 200mg/kg or ethylnitrosourea (ENU) at 10 and 40mg/kg as a positive control. Because 4 out of 6 animals at 200mg/kg of Aza died 3days after the dosing, this dose group was excluded for analyses. The frequencies of Pig-a mutants in RBCs and reticulocytes (RET) were evaluated once a week for 4 weeks after the treatment. With a single exposure to ENU, the frequencies of Pig-a mutants in both RBCs and RETs increased in a time- and dose-dependent manner. In contrast, with Aza small effects that were not statistically significant were observed in rats at 21 and 14days in the RBC Pig-a and PIGRET assays respectively. Based on the present results, the mutagenic potential of Aza is negligible after single oral administration in rats.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Reticulocytes / Azathioprine / Erythrocytes / Membrane Proteins / Mutagenicity Tests / Mutagens Limits: Animals Language: En Journal: Mutat Res Genet Toxicol Environ Mutagen Year: 2016 Document type: Article Affiliation country: Japón Country of publication: Países Bajos

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Reticulocytes / Azathioprine / Erythrocytes / Membrane Proteins / Mutagenicity Tests / Mutagens Limits: Animals Language: En Journal: Mutat Res Genet Toxicol Environ Mutagen Year: 2016 Document type: Article Affiliation country: Japón Country of publication: Países Bajos