McFee A F, Tice R R, Shelby M D
Medical Sciences Division, Oak Ridge Associated Universities, TN 37831-0117.
Mutat Res. 1992 Jan;278(1):61-8. doi: 10.1016/0165-1218(92)90286-9.
Diphenylhydantoin was tested in vivo in mice using a variety of cytogenetic endpoints to evaluate its genotoxicity. Injected doses of 125, 250 and 500 mg/kg failed to increase the number of chromosome aberrations in marrow cells at 17 h post-treatment, and 37.5, 75 and 150 mg/kg doses were likewise ineffective at 36 h. SCEs were significantly increased by doses of 125 mg/kg (but not 250 mg) after 23 h and modestly, in relation to dose, at 42 h. No increase in the number of micronuclei among marrow PCEs was seen following single i.v. injections ranging from 0.1 to 20 mg/kg. Three daily i.p. injections of doses up to 70 mg/kg also failed to increase the number of micronuclei in either marrow or peripheral blood PCEs. Some cytotoxic effect was evident following relatively high doses.
使用多种细胞遗传学终点在小鼠体内对苯妥英进行了测试,以评估其遗传毒性。在治疗后17小时,注射剂量为125、250和500mg/kg未能增加骨髓细胞中的染色体畸变数量,在36小时时,37.5、75和150mg/kg剂量同样无效。在23小时后,125mg/kg剂量(但不是250mg)显著增加了姐妹染色单体交换,在42小时时,与剂量相关有适度增加。单次静脉注射剂量为0.1至20mg/kg后,骨髓嗜多染红细胞中的微核数量未见增加。每天腹腔注射三次,剂量高达70mg/kg,也未能增加骨髓或外周血嗜多染红细胞中的微核数量。相对高剂量后有一些细胞毒性作用明显。