Accumulation of purine catabolites in solid tumors exposed to therapeutic hyperthermia |
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Authors: | M Busse P Vaupel |
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Institution: | (1) Institute of Physiology and Pathophysiology, University of Mainz, Duesbergweg 6, D-55099 Mainz, (Germany) |
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Abstract: | 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: 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. |
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Keywords: | Tumor hyperthermia ATP degradation purine catabolism hypoxanthine xanthine uric acid reactive oxygen species tumor acidosis |
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