Basic Studies on Prediction of Adverse Reactins to Pyrimidine Anti-Cancer Drugs-Analyses on Pyrimidine Metaboism Disonders-

1.二氢嘧啶酶基因组DNA的分析二氢嘧啶酶基因组DNA有10个外显子，需要复杂的操作步骤。结论：1.我们可以从外周血中分离出信使核糖核酸，亚克隆后，我们对其进行了测序。我们在二氢嘧啶尿症患者中发现了已报道的突变，提示该方法具有临床应用价值。我们分析了两例氟尿嘧啶严重中毒患者的二氢嘧啶脱氢酶基因。并发现了新的突变。患者1有1003G→T)突变和1156G→T突变。我们诊断患者患有DPD，并推测这些突变与严重的氟尿嘧啶中毒有关。患者2有1626A→G突变，但我们无法阐明该突变与严重的氟尿嘧啶中毒之间的关系。

1. Analysis on dihydropyrimidinase mRNAAnalysis on the dihydropyrimidinase genomic DNA needs complicated procedures because it has 10 exons. We could separated mRNA from peripheral blood, using ISOGEN.After subcloned, we sequenced cDNA.We identified the reported mutations In the patient with dihydropyrimidinuria, suggesting that this method is clinically useful.2. Analysis on dihydropyrimidine dehydrogenase in two patient with a severe fluorouracil toxicityWe analysed the dihydropyrimidine dehydrogenase gene in two patient with a severe fluorouracil toxicity. and identified novel mutations. The patient 1 had a 1003G→T) mutation and a 1156G→Tmutation. We diagnosed the patient as having DPD deflciency, and supeculated that these mutations were associated with a severe fluorouracil toxicity.The patient 2 had a 1626A→G mutation, but we could not clarify the relationship between this mutation and a severe fluorouracil toxicity.