Missing neutral DNase activity in lymphocytes and phytohemagglutinin-stimulated lymphocytes after high dose methotrexate therapy.
After high dose methotrexate (CAS 59-05-2) therapy of children with non-metastatic osteosarcoma the neutral DNase activity is missing in lymphocytes and in phytohemagglutinin (PHA)-stimulated lymphocytes. The neutral DNase activity reappeared in lymphocytes 14 days and in PHA-stimulated lymphocytes 10 days after the end of therapy. The DNA polymerase activity is low when neutral DNase is missing and increases when neutral DNase activity reappeared. The neutral DNase activity in lymphocytes and in PHA-stimulated lymphocytes is probably identical with DNase I. Drug induced changes in DNA conformation can enhance DNase I cleavage rate. It is assumed, that high dose methotrexate alters DNA conformation and therefore binds DNase I; after this, free DNase I is no more detectable.
Reitz
M
M
Department of Physiological Chemistry, University of Mainz, Fed. Rep. of Germany.
Gutjahr
P
P
D000293:Adolescent; D001859:Bone Neoplasms / Q000097:blood / Q000188:drug therapy; D002648:Child; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism; D003851:Deoxyribonucleases / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects*; D008214:Lymphocytes / Q000201:enzymology*; D008297:Male; D008727:Methotrexate / Q000009:adverse effects* / Q000627:therapeutic use; D012516:Osteosarcoma / Q000097:blood / Q000188:drug therapy
D004259:DNA-Directed DNA Polymerase; D003851:Deoxyribonucleases; D008727:Methotrexate