Plappert-Helbig Ulla, Junker-Walker Ursula, Martus Hans-Joerg
Novartis Institutes for BioMedical Research, Novartis Pharma AG, Switzerland.
Novartis Institutes for BioMedical Research, Novartis Pharma AG, Switzerland.
Mutat Res Genet Toxicol Environ Mutagen. 2015 Jul;786-788:120-4. doi: 10.1016/j.mrgentox.2015.04.009. Epub 2015 Apr 17.
As a part of the Japanese Center for the Validation of Alternative Methods (JaCVAM)-initiative international validation study of the in vivo rat alkaline comet assay (comet assay), we examined methyl methanesulfonate, 2,6-diaminotoluene, and 5-fluorouracil under coded test conditions. Rats were treated orally with the maximum tolerated dose (MTD) and two additional descending doses of the respective compounds. In the MMS treated groups liver and stomach showed significantly elevated DNA damage at each dose level and a significant dose-response relationship. 2,6-diaminotoluene induced significantly elevated DNA damage in the liver at each dose and a statistically significant dose-response relationship whereas no DNA damage was obtained in the stomach. 5-fluorouracil did not induce DNA damage in either liver or stomach.
作为日本替代方法验证中心（JaCVAM）发起的体内大鼠碱性彗星试验（彗星试验）国际验证研究的一部分，我们在编码测试条件下检测了甲磺酸甲酯、2,6 -二氨基甲苯和5 -氟尿嘧啶。给大鼠口服各化合物的最大耐受剂量（MTD）以及另外两个递减剂量。在甲磺酸甲酯处理组中，肝脏和胃在每个剂量水平均显示出DNA损伤显著升高，且存在显著的剂量 - 反应关系。2,6 -二氨基甲苯在每个剂量下均诱导肝脏中的DNA损伤显著升高，且存在统计学上显著的剂量 - 反应关系，而在胃中未观察到DNA损伤。5 -氟尿嘧啶在肝脏和胃中均未诱导DNA损伤。
