کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5528766 | 1548559 | 2016 | 5 صفحه PDF | دانلود رایگان |
- As a part of a collaborative study, Pig-a assay of azathioprine was investigated.
- Positive control, ENU showed significant result in both RBC Pig-a and PIGRET assays.
- Azathioprine did not increase Pig-a mutant frequency in both assays.
- The mutagenicity of azathioprine was negligible in rats with single dose.
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 200Â mg/kg or ethylnitrosourea (ENU) at 10 and 40Â mg/kg as a positive control. Because 4 out of 6 animals at 200Â mg/kg of Aza died 3Â days 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 14Â days 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.
Journal: Mutation Research/Genetic Toxicology and Environmental Mutagenesis - Volume 811, 15 November 2016, Pages 60-64