Nunn J W, Davies J E, Chipman J K
School of Biochemistry, University of Birmingham, Edgbaston, UK.
Mutat Res. 1997 Jan 3;373(1):67-73. doi: 10.1016/s0027-5107(96)00190-x.
Incubation of both rat and mouse hepatocytes with 3-chloro-4-(dichloromethyl)-5-hydroxy-2[5H]-furanone (MX) in vitro resulted in a dose-dependent increase in unscheduled DNA synthesis (UDS) at sub-cytotoxic concentrations (1-10 microM MX; 20 h incubation). Depletion of glutathione stores by pre-treatment of rat hepatocytes with buthionine sulfoximine did not result in a significant increase in UDS produced by MX. In contrast, MX did not induce UDS in mouse hepatocytes ex vivo either 3 or 16 h following administration of a single oral dose of 100 mg/kg MX. Despite the ability of MX to produce repairable DNA damage, restricted access of MX to the liver may prevent a measurable UDS response in vivo.
在体外，用3-氯-4-（二氯甲基）-5-羟基-2[5H]-呋喃酮（MX）孵育大鼠和小鼠肝细胞，在亚细胞毒性浓度（1-10 microM MX；孵育20小时）下，非预定DNA合成（UDS）呈剂量依赖性增加。用丁硫氨酸亚砜胺预处理大鼠肝细胞以耗尽谷胱甘肽储备，并未导致MX产生的UDS显著增加。相比之下，在单次口服100 mg/kg MX后3小时或16小时，MX在离体小鼠肝细胞中均未诱导UDS。尽管MX有能力产生可修复的DNA损伤，但MX进入肝脏的受限可能会阻止体内可测量的UDS反应。
