Structure-function dependence and allopurinol inhibition of ratiosensitizer/nitroreductase interaction: approaches to improving therapeutic rations
Journal Article
·
· Cancer Clin. Trials; (United States)
OSTI ID:5298358
Normal tissue toxicity of nitroaromatic radiosensitizers may originate in radiosensitizer/nitroreductase interaction. A study of two mammalian cell nitroreductases, xanthine oxidase and NADH cytochrome c reductase, shows that the efficiency of electron transfer is dependent on sensitizer electron affinity and not lipid solubility. Misonidazole and its demethylated metabolite (RO-05-9963), for example, are equally efficient as electron acceptors from xanthine oxidase. The only exception to the electron affinity correlation is m-nitrobenzamidine hydrochloride xanthine oxidase from its cofactor, xanthine. Allopurinol inhibits electron transfer and might be a useful adjuvant to the nitroreductases in vivo is deduced from the observation that allopurinol significantly alters the serum lifetimes in mice of misonidazole and RO-05-9963.
- Research Organization:
- Cross Cancer Inst., Edmonton, Canada
- OSTI ID:
- 5298358
- Journal Information:
- Cancer Clin. Trials; (United States), Journal Name: Cancer Clin. Trials; (United States) Vol. 3:1; ISSN CCTRD
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
550604* -- Medicine-- Unsealed Radionuclides in Therapy-- (1980-)
62 RADIOLOGY AND NUCLEAR MEDICINE
ANIMAL CELLS
ANIMALS
ANTINEOPLASTIC DRUGS
BIOLOGICAL EFFECTS
COENZYMES
CYTOCHROMES
DRUGS
ELECTRON TRANSFER
ENZYMES
HETEROCYCLIC COMPOUNDS
INHIBITION
MAMMALS
NADH2
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
OXIDOREDUCTASES
PIGMENTS
PURINES
RADIOSENSITIZERS
VERTEBRATES
XANTHINES
62 RADIOLOGY AND NUCLEAR MEDICINE
ANIMAL CELLS
ANIMALS
ANTINEOPLASTIC DRUGS
BIOLOGICAL EFFECTS
COENZYMES
CYTOCHROMES
DRUGS
ELECTRON TRANSFER
ENZYMES
HETEROCYCLIC COMPOUNDS
INHIBITION
MAMMALS
NADH2
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
OXIDOREDUCTASES
PIGMENTS
PURINES
RADIOSENSITIZERS
VERTEBRATES
XANTHINES