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Evaluation of the RBC Pig-a assay and the PIGRET assay using benzo[a]pyrene in rats.
Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis ( IF 2.3 ) Pub Date : 2016 Nov 15 , DOI: 10.1016/j.mrgentox.2016.03.010
Ryuta Kikuzuki 1 , Haruka Sato 1 , Ai Fujiwara 1 , Tomoko Takahashi 1 , Yosuke Ogiwara 1 , Mihoko Sugiura 1
Affiliation  

The red blood cell (RBC) Pig-a assay has the potential to detect the in vivo mutagenicity of chemicals. Recently, use of the Pig-a assay with reticulocytes (the PIGRET assay) reportedly enabled the in vivo mutagenicity of chemicals to be detected earlier than using the RBC Pig-a assay. To evaluate whether the PIGRET assay is useful and effective as a short-term test, compared with the RBC Pig-a assay, we performed both assays using benzo[a]pyrene (BP), which is a well-known mutagen. BP was used to dose 8-week-old male rats orally at 0, 75.0, 150, and 300mg/kg administered as a single administration. Peripheral blood samples were then collected on days 0, 7, 14, and 28 after treatment and were used in both assays. In the treatment groups receiving 150mg/kg of BP or more, both the RBC Pig-a assay and the PIGRET assay detected the in vivo mutagenicity of BP. In the 300mg/kg treatment group, in which a significant increase in the mutant frequency (MF) was observed at all the sampling points using both the RBC Pig-a assay and the PIGRET assay, the reticulocyte (RET) Pig-a MF was higher than the RBC Pig-a MF on days 7 and 14 after treatment; nevertheless, the negative control RET Pig-a MF was comparable to the negative control RBC Pig-a MF. In addition, the RET Pig-a MF began to increase after day 7 and reached a maximum value on day 14 after treatment, whereas the RBC Pig-a MF increased continuously from day 7 until day 28 after treatment. These results indicate that the PIGRET assay has a higher sensitivity than the RBC Pig-a assay and that the PIGRET assay is useful for the earlier detection of the in vivo mutagenicity of chemicals, compared with the RBC Pig-a assay.

中文翻译:

在大鼠中使用苯并 [a] 芘对 RBC Pig-a 测定和 PIGRET 测定进行评估。

红细胞 (RBC) Pig-a 检测有可能检测化学物质的体内致突变性。最近,据报道使用具有网织红细胞的 Pig-a 检测(PIGRET 检测)能够比使用 RBC Pig-a 检测更早地检测到化学物质的体内致突变性。为了评估 PIGRET 检测作为短期测试是否有用和有效,与 RBC Pig-a 检测相比,我们使用苯并 [a] 芘 (BP)(一种众所周知的诱变剂)进行了两种检测。BP 用于以 0、75.0、150 和 300mg/kg 的剂量口服给药 8 周龄雄性大鼠,作为单次给药。然后在治疗后的第 0、7、14 和 28 天收集外周血样本,并用于两种测定。在接受 150mg/kg 或更多 BP 的治疗组中,RBC Pig-a 试验和 PIGRET 试验均检测到 BP 的体内致突变性。在 300mg/kg 处理组中,使用 RBC Pig-a 检测和 PIGRET 检测在所有采样点观察到突变频率 (MF) 显着增加,网织红细胞 (RET) Pig-a MF 是治疗后第 7 天和第 14 天高于 RBC Pig-a MF;尽管如此,阴性对照 RET Pig-a MF 与阴性对照 RBC Pig-a MF 相当。此外,RET Pig-a MF在第7天后开始增加,并在治疗后第14天达到最大值,而RBC Pig-a MF从治疗后第7天至第28天持续增加。
更新日期:2017-01-31
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