Absence of hypoxanthine:guanine phosphoribosyltransferase activity in murine Dunn osteosarcoma.
The transplantable murine Dunn osteosarcoma has no detectable hypoxanthine:guanine phosphoribosyltransferase (EC 2.4.2.8) activity. This was established from the tumors directly and from tissue culture cell lines derived from the tumor using a variety of assays: e.g., no [3H]hypoxanthine uptake into tumor or tissue culture cells, no conversion of [3H]hypoxanthine to [3H]IMP by cell extracts from tumors or tissue culture cells, no growth of tissue culture cells in hypoxanthine:aminopterin:thymidine medium, and normal growth of these cells in 10 microM 6-mercaptopurine. Ten human osteosarcomas have been assayed, and two have no apparent hypoxanthine:guanine phosphoribosyltransferase enzyme activity. After high-dose methotrexate treatment in vivo, murine tumors could be selectively killed and normal tissues could be spared by using a rescue regimen of hypoxanthine-thymidine-allopurinol.
D000818:Animals; D002250:Carbon Radioisotopes; D002460:Cell Line; D005561:Formates / Q000378:metabolism; D019271:Hypoxanthine; D007041:Hypoxanthine Phosphoribosyltransferase / Q000172:deficiency*; D007042:Hypoxanthines / Q000378:metabolism; D007700:Kinetics; D051379:Mice; D008815:Mice, Inbred Strains; D012516:Osteosarcoma / Q000201:enzymology*; D012513:Sarcoma, Experimental / Q000201:enzymology
D002250:Carbon Radioisotopes; D005561:Formates; D007042:Hypoxanthines; C030544:formic acid; D019271:Hypoxanthine; D007041:Hypoxanthine Phosphoribosyltransferase