Suppression of Deoxyguanosine Cytotoxicity and Deoxyguanosine Kinase Activity in Mouse FM3A Mammary Carcinoma Cell : Mutants Defective in Hypoxanthine Phosphoribosyl-transferase

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The cytotoxic effect of deoxyguanosine was examined in various cell clones isolated from cultured mouse FM3A mammary carcinoma cells. The inhibitory effect of deoxyguanosine on the growth of the wild-type cell was suppressed by the addition of hypoxanthine to the culture medium. Cell mutants defective in hypoxanthine phosphoribosyl-transferase (Hprt^- mutants) were approximately 20 times less sensitive to deoxyguanosine. But the sensitivity of the Hprt^+ revertants was restored and has become close to that of the wild-type cell. Both uptake and incorporation of [^3H]-hypoxanthine and [^3H]-deoxyguanosine did not occur in the cellular acid-soluble and insoluble fractions in Hprt^- mutants but they were restored in all Hprt^+ revertants. When the activities of deoxyguanosine kinase were measured immediately after preparation of the cell-free extracts from the Hprt^- mutants, it was negligible but activity comparable to that of the wild-type appeared after dialysis of the extract. These results are explained by assuming accumulation of purine metabolite in Hprt^- mutants which inhibited the deoxyguanosine salvage pathway.
東海大学の論文