Krishna G, Nath J, Petersen M, Ong T
Division of Respiratory Disease Studies, National Institute for Occupational Safety and Health, Morgantown, WV 26505-2888.
Mutat Res. 1988 Feb;204(2):297-305. doi: 10.1016/0165-1218(88)90103-6.
In several acute and chronic exposures to various chemicals in vivo and in vitro, the average sister-chromatid exchange (SCE) frequencies in human, mouse, rat, and rabbit lymphocytes generally decrease with time following treatment. The rate of this decline varies, but little data have been published pertaining to the comparative kinetics of SCEs both in vivo and in vivo/in vitro (exposure of animals to the test compound and culturing of cells) simultaneously in the same tissues. In this study, a single dose of cyclophosphamide (40 mg/kg) was injected for varying periods (6-48 h) and its effects, as assessed by the induction of SCEs, were analyzed under both in vivo and in vivo/in vitro conditions in mouse bone marrow and spleen cells. In vivo, the cyclophosphamide-induced SCEs increased with increasing time up to 12 h, stayed at approximately the same level until 24 h, and then decreased with increase in post-exposure time. However, the SCE levels remained significantly higher than controls at 48 h post-exposure time in both bone marrow and spleen cells. Under in vivo/in vitro conditions, the SCEs in bone marrow decreased with increase in post-exposure time until reaching control values by 48 h post exposure. However, in spleen cells, the decrease in SCE level was gradual, and by 48 h post-exposure time, the cells still had approximately 6 times higher SCEs than the control values. These results suggest that there are pharmacokinetic differences for cyclophosphamide in mouse bone marrow and spleen. Also, there is a differential SCE response to cyclophosphamide under in vivo and in vivo/in vitro conditions.
在体内和体外对多种化学物质进行的多次急性和慢性暴露实验中，人、小鼠、大鼠和兔淋巴细胞中的平均姐妹染色单体交换（SCE）频率通常在处理后的一段时间内随时间下降。这种下降速率各不相同，但关于在同一组织中同时进行体内和体内/体外（动物接触受试化合物并培养细胞）SCEs比较动力学的相关数据发表较少。在本研究中，对小鼠注射单剂量环磷酰胺（40mg/kg），持续不同时间（6 - 48小时），并在体内和体内/体外条件下，分析其对小鼠骨髓和脾细胞中SCE诱导作用的影响。在体内，环磷酰胺诱导的SCEs在12小时内随时间增加，直至24小时保持在大致相同水平，然后随着暴露后时间的增加而下降。然而，在暴露后48小时，骨髓和脾细胞中的SCE水平仍显著高于对照组。在体内/体外条件下，骨髓中的SCEs随着暴露后时间的增加而下降，直至暴露后48小时达到对照值。然而，在脾细胞中，SCE水平下降较为缓慢，在暴露后48小时，细胞的SCEs仍比对照值高约6倍。这些结果表明，环磷酰胺在小鼠骨髓和脾中的药代动力学存在差异。此外，在体内和体内/体外条件下，对环磷酰胺的SCE反应也存在差异。
