6533b861fe1ef96bd12c4628

RESEARCH PRODUCT

Accumulation of purine catabolites in solid tumors exposed to therapeutic hyperthermia

P. VaupelM. Busse

subject

Inosine monophosphatePurineGuanosine MonophosphateGuanosineGuanosine triphosphateModels BiologicalCellular and Molecular Neurosciencechemistry.chemical_compoundAdenosine TriphosphateInosine MonophosphateNeoplasmsmedicineAnimalsHumansInosineMolecular BiologyHypoxanthinePharmacologyHyperthermia InducedNeoplasms ExperimentalCell BiologyRibonucleotidesXanthineBiochemistrychemistryPurinesMolecular MedicineUric acidGuanosine Triphosphatemedicine.drug

description

Intensified adenosine triphosphate (ATP) degradation following therapeutic hyperthermia is often observed in solid tumors. As a result, accumulation of purine catabolites can be expected together with formation of protons at several stages during degradation to the final product, uric acid. Proton formation in turn can contribute to the development of heat-induced acidosis. Furthermore, oxidation of hypoxanthine and xanthine may result in generation of reactive oxygen species, which may lead to DNA damage, lipid peroxidation and protein denaturation, thus also contributing to heat-induced cytotoxicity. In hyperthermia experiments a tumor-size-dependent, significant increase in the levels of the following catabolites has been demonstrated: [symbol: see text] [IMP + GMP] (sum of guanosine and inosine monophosphate levels), inosine, hypoxanthine, xanthine and uric acid, along with a drop in ATP and guanosine triphosphate (GTP) levels. These data suggest that formation of reactive oxygen species and protons during purine degradation may indeed play a significant role in the antitumor effect of hyperthermia.

yearjournalcountryeditionlanguage
1996-05-15Experientia
https://doi.org/10.1007/bf01919318