Absence of hypoxanthine:guanine phosphoribosyltransferase activity in murine Dunn osteosarcoma

Cancer Res. 1983 Sep;43(9):4098-101.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Carbon Radioisotopes
  • Cell Line
  • Formates* / metabolism
  • Hypoxanthine
  • Hypoxanthine Phosphoribosyltransferase / deficiency*
  • Hypoxanthines / metabolism
  • Kinetics
  • Mice
  • Mice, Inbred Strains
  • Osteosarcoma / enzymology*
  • Sarcoma, Experimental / enzymology

Substances

  • Carbon Radioisotopes
  • Formates
  • Hypoxanthines
  • formic acid
  • Hypoxanthine
  • Hypoxanthine Phosphoribosyltransferase