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

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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.