As part of a collaborative study in the Mammalian Mutagenicity Study (MMS) Group of the Japanese Environmental Mutagen Society (JEMS), we investigated the in vivo genotoxicity profile of 1,2-dimethylhydrazine (DMH) using a Pig-a assay in total red blood cells (RBC Pig-a assay) or a reticulocyte Pig-a assay (PIGRET assay). We also assessed the genotoxic potential of DMH using both a bone marrow micronucleus test and a liver comet assay as follow-up studies. Single administration of 25, 50, 100mg/kg DMH to male rats did not show time- or dose-related increases in Pig-a mutant frequency (MF) in either the RBC Pig-a or PIGRET assays up to 4 weeks after treatment. The bone marrow micronucleus test under the same dose levels was judged positive, while the liver comet assay was judged inconclusive due to the high number of hedgehogs. Re-evaluation of the rat liver comet assay at lower dose levels (4, 10, and 25mg/kg DMH) showed a dose-related increase in%DNA in tail. Taken together, DMH showed a positive response in both the bone marrow micronucleus test and liver comet assay, while the increases in Pig-a MF in both the RBC Pig-a and PIGRET assays could hardly be detected after single dosing. These results suggest that DMH provides different genotoxicity outcomes depending on the endpoint following acute in vivo dosing.

中文翻译：

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在 1,2-二甲基肼单剂量研究中使用抗大鼠红细胞标记 HIS49 抗体进行大鼠 Pig-a 检测的报告。

作为日本环境诱变剂协会 (JEMS) 哺乳动物致突变性研究 (MMS) 小组合作研究的一部分，我们使用 Pig-a 测定法研究了 1,2-二甲基肼 (DMH) 的体内遗传毒性血细胞（RBC Pig-a 检测）或网织红细胞 Pig-a 检测（PIGRET 检测）。我们还使用骨髓微核试验和肝彗星试验作为后续研究评估了 DMH 的遗传毒性潜力。在 RBC Pig-a 或 PIGRET 试验中，雄性大鼠单次给予 25、50、100mg/kg DMH 未显示在治疗后长达 4 周的时间或剂量相关的 Pig-a 突变频率 (MF) 增加。相同剂量水平下的骨髓微核试验判定为阳性，而肝彗星试验因刺猬数量较多而判定为不确定。在较低剂量水平（4、10 和 25mg/kg DMH）下对大鼠肝彗星试验的重新评估显示尾部 DNA 百分比随剂量相关增加。综上所述，DMH 在骨髓微核试验和肝彗星试验中均显示出阳性反应，而单次给药后几乎无法检测到 RBC Pig-a 和 PIGRET 试验中 Pig-a MF 的增加。这些结果表明，根据急性体内给药后的终点，DMH 提供不同的遗传毒性结果。