Purine metabolism was examined in a clonal line of mouse neuroblastoma cells resistant to the cytotoxic effects of 6 thioguanine. Comparative studies in the resistant and parental lines indicate that the former cells have less than 1% of normal hypoxanthine phosphoribosyltransferase activity. The activities of other enzymes important in the de novo and salvage pathways of purine biosynthesis were not significantly different in the 2 lines. Hypoxanthine phosphoribosyltransferase deficiency in this neuroblastoma line was associated with increased intracellular concentrations of 5 phosphoribosyl 1 pyrophosphate, an increased rate of purine biosynthesis de novo, and failure to incorporate hypoxanthine, but not adenine, into nucleotides. These are essentially the same alterations in purine metabolism that occur in hypoxanthine phosphoribosyltransferase deficient fibroblasts or lymphoblasts derived from individuals with the Lesch Nyhan syndrome. Clonal lines of hypoxanthine phosphoribosyltransferase deficient neuroblastoma cells may therefore be of use in elucidating the mechanisms by which the enzyme defect leads to the neurologic dysfunction seen in children with this disease.
|Original language||English (US)|
|Number of pages||4|
|Journal||Proceedings of the National Academy of Sciences of the United States of America|
|Issue number||12 (II)|
|State||Published - Jan 1 1973|
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