Suppression of deoxyguanosine cytotoxicity and deoxyguanosine kinase activity in mouse FM3A mammary carcinoma cell: mutants defective in hypoxanthine phosphoribosyl-transferase.

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.