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Gu Zhou¹, Andrew Williams¹, Danielle P M LeBlanc¹

¹Environmental Health Science and Research Bureau, Healthy Environments and Consumer Safety Branch, 251 Sir Frederick Banting Driveway, Ottawa, Health CanadaON, K1A 0K9, Canada.

Archives of toxicology

|May 21, 2025

概括

经济合作与发展组织的测试指南488 (TG 488) 使用28+28天的暴露和采样设计来评估生殖细胞的致病性. 这项研究发现不需要更晚的采样时间,支持当前的TG 488设计.

科学领域:

毒理学毒理学毒理学
遗传学遗传学是一个
在体内进行突变性试验.

背景情况:

经济合作与发展组织的测试指南 (TG 488) 是使用转基因动物模型评估体内突变性的一种标准.
TG 488建议28天暴露,然后在28天后 (28+28d) 采取生殖细胞样本.

研究的目的:

评估是否需要比TG 488中的标准28+28d更长的采样时间来评估生殖细胞变异性.
确定胚胎细胞突变性评估的最佳实验设计.

主要方法:

成年 MutaMouse雄性被口服暴露于甲 (BaP),N-乙烯-N-氨酸urea (ENU),异甲硫酸盐 (iPMS),或prokarbazine (PRC) 的28天.
基因细胞的突变频率 (MF) 通过lacZ测定在暴露后的3,28,42和70天被量化.
使用基准剂量建模来分析剂量反应关系.

主要成果:

所有四种测试化学物质都在28+28d采样时间显著增加了lacZ MF.
在以后的采样时间 (42d和70d) 没有观察到MF的进一步增加.
发现28+28d设计足够,一些化学品在这个时间点表现出比较早的采样 (3d) 更强烈的反应.

结论:

在TG 488中标准的28+28d实验设计足以评估生殖细胞的变异性.
暴露后28天以后的采样时间不必用于根据TG 488.8评估生殖细胞变异性.
这些发现支持继续使用已建立的TG 488协议.

关键词:

N-乙烯-N-酸氨酸urea-N-乙烯-N-酸氨酸urea.基准剂量的基准剂量子[a]二烯是一种二烯.异烯甲硫酸盐是一种异烯甲硫酸盐.卡巴辛 (Proccarbazine) 是一种卡巴辛的药物.

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