Cairnie A B
Radiat Res. 1983 Apr;94(1):221-6.
S-2-(3-Aminopropylamino)ethylphosphorothioic acid (WR2721) has radioprotective properties, but it is also toxic--in man it causes nausea and vomiting. Since radiation also causes nausea and vomiting it is important to know whether WR2721 would increase or decrease the likelihood of nausea and vomiting after radiation. This question was investigated in rats using the phenomenon of aversion to the taste of saccharin, which is readily inducible and is understood to be controlled in rats by the same pathways that control nausea and vomiting in man. The taste aversion was induced by giving 0.2 Gy60Co gamma radiation 30 min after drinking 0.1% saccharin, or WR2721 immediately after the saccharin, or giving both radiation and WR2721. There were appropriate controls. In sham-irradiated rats, WR2721 (40 or 200 mg/kg, but not 8 mg/kg) produced a significant taste aversion. When WR2721 (40 or 200 mg/kg) was given immediately after the saccharin to irradiated rats it increased the taste aversion significantly, but it did not have any effect at 8 mg/kg. It was concluded that at doses which were optimal for radioprotection (approximately 200 mg/kg) or lower, WR2721 increased in rats the taste aversion induced by radiation. By inference if conditioned taste aversion is an appropriate paradigm, WR2721 would increase nausea and vomiting in man induced by radiation.
S-2-(3-氨丙基氨基)乙硫代磷酸（WR2721）具有辐射防护特性，但它也有毒性——在人体中会引起恶心和呕吐。由于辐射也会导致恶心和呕吐，所以了解WR2721会增加还是降低辐射后恶心和呕吐的可能性很重要。在大鼠中利用对糖精味道的厌恶现象对这个问题进行了研究，这种厌恶现象很容易诱发，并且据认为在大鼠中是由与控制人类恶心和呕吐相同的途径控制的。在饮用0.1%糖精30分钟后给予0.2 Gy 60Coγ射线辐射，或在糖精之后立即给予WR2721，或同时给予辐射和WR2721来诱发味道厌恶。设置了适当的对照组。在假照射的大鼠中，WR2721（40或200 mg/kg，但8 mg/kg无效）产生了显著的味道厌恶。当在给辐照大鼠喂食糖精后立即给予WR2721（40或200 mg/kg）时，它显著增加了味道厌恶，但8 mg/kg时没有任何效果。得出的结论是，在对辐射防护最佳的剂量（约200 mg/kg）或更低剂量下，WR2721会增加大鼠中由辐射诱发的味道厌恶。由此推断，如果条件性味道厌恶是一个合适的范例，WR2721会增加人类中由辐射诱发的恶心和呕吐。
