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.
Hyodo
M
M
Department of Molecular Biology, School of Medicine, Tokai University, Kanagawa, Japan.
Suzuki
K
K
Tsuda
M
M
D000818:Animals; D003849:Deoxyguanosine / Q000494:pharmacology*; D019271:Hypoxanthine; D007041:Hypoxanthine Phosphoribosyltransferase / Q000172:deficiency / Q000235:genetics; D007042:Hypoxanthines / Q000494:pharmacology; D008325:Mammary Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009154:Mutation; D010770:Phosphotransferases / Q000172:deficiency; D017853:Phosphotransferases (Alcohol Group Acceptor); D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000378:metabolism
D007042:Hypoxanthines; D019271:Hypoxanthine; D007041:Hypoxanthine Phosphoribosyltransferase; D010770:Phosphotransferases; D017853:Phosphotransferases (Alcohol Group Acceptor); C019165:deoxyguanosine kinase; D003849:Deoxyguanosine