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DIRECT HEAT DEATH AND HEAT POTENTIATION OF RADIATION DAMAGE IN CANCER CELLS: MODIFICATION BY INTRACELLULAR AND ENVIRONMENTAL FACTORS

This investigation represents an attempt to evaluate the damaging effects of hyperthermia on mammalian cells, specifically Bp-8 murine sarcoma cells. Two types of heat damage were studied, thermal radiosensitization and direct thermal cell death. The experiments were designed to answer two fundamental questions: (1) Do thermal radiosensitization and direct thermal death share a common lesion? (2) What are the factors responsible for the enhanced thermal sensitivity of tumors as compared to normal body cells? / (I) Three types of experiments provided evidence against a common mode of action for thermal radiosensitization and direct thermal death. (1) Evaluation of kinetics of heat and radiation death. (2) Thermal radiosensitization and direct heat death as a function of heating time. (3) Independent modification of radiosensitization and thermal death. / (II) Although the two types of heat damage do not share the same mode of action, the two effects show certain common features and one is the fact that tumors are more sensitive to heat than normal body cells. This enhanced thermal sensitivity of tumors may be due to (a) poorly oxygenated regions (hypoxia) in tumors which unable them to deal with the adverse consequences of hyperthemia. (b) hypoxia may enhance tumor glycolysis, in turn cause tumor acidification and reduce the resistance of acidified cells. / To evaluate the influence of these factors on thermal response of cells, a method was developed to permit independent variation of cell pH and environmental oxygen. Experiments on the effects of cellular acidification indicated that reduced intracellular pH and not reduced environmental pH causes pronounced enhancement of thermal damage. Studies on the effect of acute hypoxia on thermal sensitization indicated that thermal radiosensitization and direct thermal death is the same for both euoxic and hypoxic cells. / In conclusion, it appears that hypoxia indued tumor acidification rather than hypoxia per se is responsible for the enhanced thermal sensitization of tumors. Moreover, the degree of thermal sensitization is proportional to the degree of intracellular and not environmental acidification. / Source: Dissertation Abstracts International, Volume: 42-06, Section: B, page: 2256. / Thesis (Ph.D.)--The Florida State University, 1981.

Identiferoai:union.ndltd.org:fsu.edu/oai:fsu.digital.flvc.org:fsu_74555
ContributorsMIVECHI, NAHID FATEME., Florida State University
Source SetsFlorida State University
Detected LanguageEnglish
TypeText
Format133 p.
RightsOn campus use only.
RelationDissertation Abstracts International

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