Effect of Methotrexate on Purine Salvage Enzyme Activity in L1210 cells in vivo

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Purine salvage enzymes (ADA, PNP, HGPRT) are important in lymphocyte differentiation and proliferation. But the effect of antineoplastic agents on purine metabolism is poorly understood. We studied in vivo effects of several antineoplastic agents on these enzyme activities in L1210 mouse leukemic cells. L1210 cells were injected into peritoneal space of BDF/1mouse, followed by antineoplastic agent at 6-7 days later. After 6 hrs of exposure to MTX, ADA activity and PNP activity were slightly inhibited. On the contrary, HGPRT activity was activated remarkably. Daunorubicin inhibited PNP activity slightly but it had no effect on ADA activity and HGPRT activity. Coformycin inhibited ADA activity severely but it had no effect on PNP and HGPRT activity. These observation suggest that the block of de novo purine synthesis may result in reduced activity of purine interconversion enzyme and activated purine salvage synthesis. But further study is needed.
Japanese Society of Gout and Nucleic Acid Metabolismの論文