Chemical inactivation of prion

朊病毒去污需要非常苛刻的处理，如浸泡在浓氢氧化钠、次氯酸钠或在134℃下高压灭菌，以消除所有传染性。但就医疗设备的日常消毒而言，被污染物质的传染性滴度相对较低。因此，一个温和的去污程序就足够了，这样被污染的材料就不会被严重的化学或物理处理破坏。发现液体环氧乙烷（LEO）对1%痒鼠脑匀浆的朊病毒传染性有剂量依赖性降低，用2%的环氧乙烷（LEO）在25℃下处理40 h，降低率可达10^<-5>以上。然而，LEO很难处理，需要较长时间才能使朊病毒失活。因此，我们筛选了三种环氧化合物，β-丙内酯、环氧丙烷和甘油三酯（GLD），它们的结构与EO相似，但比LEO更容易处理。在这些化学物质中，GLD最有效地将朊病毒蛋白分解成小片段。根据生物测定结果，在室温下，3% GLD处理5小时，5% GLD处理2、5小时或12小时，平均孵育时间分别延长了44、30、110和73天。根据剂量-孵育时间标准曲线，估计感染性滴度下降为10a^<-3>或更多。因此，GLD对朊蛋白的降解降低了瘙痒病的传染性。pH值在8左右，加入0.15 M NaCl等盐，温度在50℃左右，可以增强GLD的效果。然而，目前还没有小鼠生物测定方法。

Prion decontamination requires very harsh treatment such as soaking in concentrated sodium hydroxide, sodium hypochlorite or autoclaving at 134℃ to eliminate all infectivity. However, as Iong as the daily disinfection of medical equipment is concerned, the infectivity titer of the contaminated materials is relatively low. Therefore, a mild decontamination procedure would be adequate so that contaminated materials are not damaged by severe chemical or physical treatments. Liquid ethylene oxide (LEO) was found to cause a dose-dependent decrease in prion infectivity in 1% scrapie-mouse brain homogenates, and the reduction attained by treatment with 2% LEO at 25℃ for 40 h reached more than 10^<-5>. LEO is, however, difficult to handle and takes relatively long time to inactive prion. Therefore, we screened three epoxides, β-propiolactone, propylene oxide, and glycidol (GLD), which resemble to EO in their structures but are easier in handling than LEO.Among these chemicals, GLD worked most effectively and degraded prion protein into small fragments. As a result of the bioassay, treatment with 3% GLD for 5 hr and 5% GLD for 2, 5 hr or 12 hr at room temperature prolonged the mean incubation time by 44, 30, 110 and 73 days, respectively. From dose-incubation time standard curve, the decrease in infectivity titers was estimated as 10a^<-3> or more. Therefore, degradation of prion protein by GLD decreased the scrapie infectivity. Effect of GLD was enhanced by high pH around 8 and presence of some salt such as 0.15 M NaCl together with higher temperature of 50℃. However, the mouse-bioassay are not available at present.