Biophysical aspects of the integrated combination of cytostatic drugs with radiotherapy. Part 1: In vitro investigations on the kinetics of activated isophosphamide metabolites and the determination of selective properties of DNA-interstrand and DNA-protein crosslinking mechanisms using 31P-NMR spectroscopy.
The pH dependence of the kinetics of the "activated" isophosphamide metabolites 4-hydroxy-isophosphamide, isoaldophosphamide and isophosphoramide mustard has been characterized with the help of 31P-NMR Fourier spectroscopy. The most outstanding feature is the pH-dependence of the decay kinetics of 4-hydroxy-isophosphamide and isoaldophosphamide yielding the alkylating moiety isophosphoramide mustard and acrolein. With the same spectroscopic technique the alkylation of biomolecules containing guanine (cGMP, GDP, GTP, synthetic oligodeoxynucleic acid serving as a surrogate of DNA) and proteins containing cysteine as receptor molecule have been analyzed. The kinetic data provide information on combining the measured substrates with radiotherapy to be presented in further communications.
Ulmer
W
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FB Radiologie, Bereich Medizinphysik/Biophysik, St.-Marien-Krankenhaus, Siegen.
D000478:Alkylation; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D055592:Biophysical Phenomena; D001703:Biophysics; D003131:Combined Modality Therapy; D003432:Cross-Linking Reagents / Q000494:pharmacology*; D004273:DNA, Neoplasm / Q000737:chemistry / Q000187:drug effects*; D006207:Half-Life; D007069:Ifosfamide / Q000032:analysis / Q000737:chemistry / Q000493:pharmacokinetics*; D007939:Leukemia L1210 / Q000188:drug therapy / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D009363:Neoplasm Proteins / Q000737:chemistry / Q000187:drug effects*; D011355:Prodrugs / Q000032:analysis / Q000737:chemistry / Q000493:pharmacokinetics*; D011878:Radiotherapy; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D000970:Antineoplastic Agents; D003432:Cross-Linking Reagents; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D011355:Prodrugs; D007069:Ifosfamide