Tomioka S, Nakajo N
Department of Dental Anesthesiology, School of Dentistry, University of Tokushinma, Japan.
Acta Anaesthesiol Scand. 2000 Nov;44(10):1261-5. doi: 10.1034/j.1399-6576.2000.441013.x.
In spite of its high placental transfer, propofol is frequently used in general anesthesia and sedation during obstetric and gynecological surgery such as in vitro fertilization. This study investigated whether or not propofol has a genotoxic potential by the sister chromatid exchange assay in vitro.
Sister chromatid exchanges induced after exposure to propofol were measured in Chinese hamster ovary cells with and without metabolic activation. After propofol (0.2-20 microg ml(-1)) diluted dimethyl sulfoxide was applied for 2 h with or without S9 mix, the cells having been incubated for two metaphases (34 h) in the presence of 5'-bromo-2-deoxyuridine. N-nitrosodimethylamine and mitomycin C were used as positive controls with and without metabolic activation. The chromosomes were stained with the fluorescence plus Giemsa method, and then sister chromatid exchanges in 50 cells were counted for each concentration.
Although increasing concentrations of propofol inhibited cell proliferation, no concentrations of propofol used in this study increased the sister chromatid exchange values, with and without metabolic activation.
It was concluded that there was no indication, from the sister chromatid exchange assay in mammalian cells, of a genotoxic effect of propofol and its metabolites.
尽管丙泊酚具有较高的胎盘转运率，但它仍频繁用于产科和妇科手术（如体外受精）的全身麻醉和镇静。本研究通过体外姐妹染色单体交换试验，调查丙泊酚是否具有遗传毒性潜力。
在有和没有代谢活化的情况下，测量丙泊酚暴露后中国仓鼠卵巢细胞中诱导的姐妹染色单体交换。在用或不用S9混合物的情况下，将稀释于二甲基亚砜中的丙泊酚（0.2 - 20微克/毫升）作用2小时，细胞已在5'-溴-2-脱氧尿苷存在下孵育两个中期（34小时）。N-亚硝基二甲胺和丝裂霉素C用作有和没有代谢活化的阳性对照。用荧光加吉姆萨法对染色体进行染色，然后对每个浓度的50个细胞计数姐妹染色单体交换情况。
尽管丙泊酚浓度增加会抑制细胞增殖，但本研究中使用的任何丙泊酚浓度在有和没有代谢活化的情况下均未增加姐妹染色单体交换值。
从哺乳动物细胞的姐妹染色单体交换试验得出的结论是，没有迹象表明丙泊酚及其代谢产物具有遗传毒性作用。
