McMurrough J, McLeod H L
Department of Medicine and Therapeutics, University of Aberdeen, Foresterhill, UK.
Br J Clin Pharmacol. 1996 May;41(5):425-7. doi: 10.1046/j.1365-2125.1996.34212.x.
Subjects with low or absent dihydropyrimidine dehydrogenase activity (DPD) are at risk of excessive toxicity or death when undergoing fluoropyrimidine chemotherapy. The DPD polymorphism has not been well characterized in the general population and the frequency of the enzyme deficiency is not known. In preparation for a population multicentre analysis of DPD activity, a comparison of sample preparation methods and a pilot study in normal volunteer subjects was performed. The stability of peripheral blood mononuclear cell DPD activity at -70 degrees C was determined in 35 mM sodium phosphate buffer with 10% glycerol, 100% fetal calf serum (FCS) or as a dry pellet. DPD activity declined in FCS and increased in glycerol buffer, both reaching a plateau value 14 days after blood sampling. The glycerol buffer method was then used to study DPD activity in 50 British subjects (36 M: 14F; 20-56 years). A 8.4-fold range in DPD activity was observed (30.4-256 pmol min-1 mg-1 protein). DPD activity was not influenced by age or cigarette smoking. This information will facilitate analysis of the DPD polymorphism in populations from different countries and ethnic groups.
二氢嘧啶脱氢酶活性（DPD）低或缺乏的患者在接受氟嘧啶化疗时存在毒性过大或死亡的风险。DPD多态性在普通人群中尚未得到充分表征，酶缺乏的频率也未知。在准备对DPD活性进行人群多中心分析时，对样本制备方法进行了比较，并在正常志愿者中进行了一项初步研究。在含有10%甘油的35 mM磷酸钠缓冲液、100%胎牛血清（FCS）或作为干燥沉淀的情况下，测定了外周血单核细胞DPD活性在-70℃时的稳定性。DPD活性在FCS中下降，在甘油缓冲液中增加，两者在采血后14天均达到稳定值。然后使用甘油缓冲液法研究了50名英国受试者（36名男性：14名女性；20 - 56岁）的DPD活性。观察到DPD活性范围为8.4倍（30.4 - 256 pmol min-1 mg-1蛋白）。DPD活性不受年龄或吸烟的影响。这些信息将有助于分析来自不同国家和种族人群的DPD多态性。
