Davies J E, Mynett K, Gescher A, Chipman J K
School of Biochemistry, University of Birmingham, Edgbaston, UK.
Mutat Res. 1993 Jun;287(2):157-64. doi: 10.1016/0027-5107(93)90009-5.
Hepatocytes from rats, mice or humans were exposed to either 2-nitropropane or propane 2-nitronate and the extent of unscheduled DNA synthesis (UDS) was measured. At a concentration of 2-nitropropane (0.1 mM) that produced a marked induction of UDS in rat hepatocytes, a negative or minimal response was seen in hepatocytes from mice and humans. A 10-fold higher concentration of 2-nitropropane was required in mouse hepatocytes for an equivalent UDS response to that seen in rat-liver cells. All three species showed UDS after exposure of hepatocytes to propane 2-nitronate at 0.1 mM although the effect in human cells was variable. In rat hepatocytes the induction of UDS by 2-nitropropane was not inhibited by the antioxidant dimethyl sulphoxide (1%). In these cells, 2-nitropropane produced an electrochemically active modified deoxynucleoside, similar to that reported to be formed in livers of rats which had received 2-nitropropane in vivo. A smaller but significant production of this altered deoxynucleoside was found in mouse hepatocytes but not in human hepatocytes treated identically. The level of 8-oxo-7,8-dihydrode-oxyguanosine was not increased in hepatocytes from any of the three species exposed to 2-NP under the same conditions. It is suggested that the UDS caused by 2-nitropropane may be in response to damage other than that produced by oxygen radicals.
将大鼠、小鼠或人类的肝细胞暴露于2-硝基丙烷或2-硝基丙烷磺酸盐中，然后测量其非预定DNA合成（UDS）的程度。在能显著诱导大鼠肝细胞UDS的2-硝基丙烷浓度（0.1 mM）下，小鼠和人类的肝细胞呈现阴性或极小的反应。在小鼠肝细胞中，需要将2-硝基丙烷的浓度提高10倍才能产生与大鼠肝细胞相当的UDS反应。当肝细胞暴露于0.1 mM的2-硝基丙烷磺酸盐时，所有三个物种的肝细胞均出现UDS，尽管在人类细胞中的效果存在差异。在大鼠肝细胞中，2-硝基丙烷对UDS的诱导作用不受抗氧化剂二甲基亚砜（1%）的抑制。在这些细胞中，2-硝基丙烷产生了一种具有电化学活性的修饰脱氧核苷，类似于在体内接受过2-硝基丙烷的大鼠肝脏中所报道形成的那种。在同样处理的小鼠肝细胞中发现了这种改变的脱氧核苷的少量但显著的产生，而在人类肝细胞中未发现。在相同条件下，暴露于2-硝基丙烷的三个物种的肝细胞中，8-氧代-7,8-二氢脱氧鸟苷的水平均未升高。有人提出，2-硝基丙烷引起的UDS可能是对除氧自由基产生的损伤之外的其他损伤的反应。
