Division of Genetic and Molecular Toxicology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, Arkansas, USA.
Environ Mol Mutagen. 2021 Nov;62(9):482-489. doi: 10.1002/em.22465. Epub 2021 Oct 27.
In order to investigate the possibility that treatment age affects the genotoxic response to ethyl methane sulfonate (EMS) exposure, we dosed gpt-delta neonatal mice on postnatal days 1-28 with 5-100 mg/kg/day of EMS and measured micronucleus (MN) induction in peripheral blood and gpt gene mutation in liver, lung, bone marrow, small intestine, spleen, and kidney. The data were compared to measurements from similarly exposed adult gpt-delta mice. Our results indicate that the peripheral blood MN frequencies in mice treated as neonates are not substantially different from those measured in mice treated as adults. There were, however, differences in tissue-specific gpt mutation responses in mice treated with EMS as neonates and adults. Greater mutant frequencies were seen in DNA isolated from kidney of mice treated as neonates, whereas the mutant frequencies in bone marrow, liver, and spleen were greater in the animals treated as adults. Benchmark dose potency ranking indicated that the differences for kidney were significant. Our data indicate that there are differences in EMS-induced genotoxicity between mice treated as adults and neonates; the differences, however, are relatively small.
为了研究处理年龄是否会影响乙基甲烷磺酸（EMS）暴露的遗传毒性反应，我们在新生后 1-28 天对 gpt-delta 新生小鼠进行了 5-100mg/kg/天的 EMS 剂量处理，并测量了外周血中的微核（MN）诱导和肝脏、肺、骨髓、小肠、脾脏和肾脏中的 gpt 基因突变。将这些数据与同样接受过 EMS 暴露的成年 gpt-delta 小鼠的测量值进行了比较。我们的结果表明，新生小鼠的外周血 MN 频率与成年小鼠的测量值没有显著差异。然而，在新生和成年小鼠中，EMS 处理后组织特异性 gpt 突变反应存在差异。在作为新生小鼠处理的肾脏中分离出的 DNA 中观察到更高的突变频率，而在成年动物中，骨髓、肝脏和脾脏中的突变频率更高。基准剂量功效排名表明，肾脏的差异是显著的。我们的数据表明，成年和新生小鼠对 EMS 诱导的遗传毒性反应存在差异；然而，这些差异相对较小。
