To evaluate the suitability of the rat Pig-a assay on reticulocytes (PIGRET assay) as a short-term test, red blood cell (RBC) Pig-a and PIGRET assays after single doses with hydroxyurea (HU) and melphalan (L-PAM) were conducted and the results of both assays were compared. HU was administered once orally to male SD rats at 250, 500 and 1000mg/kg, and both assays were conducted using peripheral blood withdrawn from the jugular vein at 1, 2 and 4 weeks after dosing. L-PAM was administered at 1.25, 2.5 and 5mg/kg in the same manner. L-PAM produced significant dose-dependent increases in mutant frequencies in the PIGRET assay after single oral doses, but did not produce dose-dependent increases in mutant frequencies in the RBC Pig-a assay. These results suggest that the PIGRET assay is more sensitive for the evaluation of the mutagenic potential of L-PAM than the RBC Pig-a assay. In contrast, HU, a clastogenic but not DNA-reactive compound, gave negative results in both assays. The results with these 2 chemicals indicate that the single-dose PIGRET assay in rats has the potential to properly detect DNA-reactive compounds that directly cause DNA damage in a short-term assay.

中文翻译：

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在大鼠中使用单剂量羟基脲和马法兰对 RBC Pig-a 和 PIGRET 测定的评估。

评估大鼠 Pig-a 试验对网织红细胞的适用性（PIGRET 试验）作为短期试验、红细胞 (RBC) Pig-a 和 PIGRET 试验在单次服用羟基脲 (HU) 和马法兰 (L-PAM) 后的适用性) 进行，并比较两种测定的结果。以 250、500 和 1000mg/kg 的剂量向雄性 SD 大鼠口服一次 HU，并且在给药后 1、2 和 4 周使用从颈静脉抽取的外周血进行这两种测定。L-PAM 以相同的方式以 1.25、2.5 和 5mg/kg 给药。在单次口服剂量后，L-PAM 在 PIGRET 试验中产生显着的剂量依赖性突变频率增加，但在 RBC Pig-a 试验中没有产生剂量依赖性突变频率增加。这些结果表明，PIGRET 试验比 RBC Pig-a 试验对 L-PAM 的致突变潜力的评估更敏感。相比之下，HU，一种致裂体但不具有 DNA 反应性的化合物，在两种检测中都给出了阴性结果。这两种化学品的结果表明，大鼠单剂量 PIGRET 试验有可能在短期试验中正确检测直接导致 DNA 损伤的 DNA 反应性化合物。