Analysis of enhancement at small and large radiation doses for effectiveness of inactivation in cultured cells by combining two agents with radiation.

Purpose: To evaluate the enhancement effect of two combined radiation-sensitizing agents in mammalian cells at small doses as compared to large doses using the linear-quadratic (LQ) mathematical model.

Methods And Materials: Data on clonogenic assays concerning the radio-enhancement effects of combined halogenated pyrimidines and hyperthermia or combined cisplatin and hyperthermia, as published in earlier reports, were analyzed according to the LQ-formula: S(D)/S(0) = exp-(αD + βD(2)). Effects of sensitizing agents on the linear parameter α and the quadratic parameter β are compared in order to evaluate differences depending on the applied dose, the possible relations to mechanisms of radiation sensitization and to derive suggestions for applications.

Dynamics of chromosomal aberrations, induction of apoptosis, BRCA2 degradation and sensitization to radiation by hyperthermia.

Hyperthermia can transiently degrade BRCA2 and thereby inhibit the homologous recombination pathway. Induced DNA-double strand breaks (DSB) then have to be repaired via the error prone non-homologous end-joining pathway. In the present study, to investigate the role of hyperthermia in genotoxicity and radiosensitization, the induction of chromosomal aberrations was examined by premature chromosome condensation and fluorescence in situ hybridisation (PCC-FISH), and cell survival was determined by clonogenic assay shortly (0-1 h) and 24 h following exposure to hyperthermia in combination with ionizing radiation.

Enhancement of radiation effectiveness by hyperthermia and incorporation of halogenated pyrimidines at low radiation doses as compared with high doses: implications for mechanisms.

Purpose: Application of the linear-quadratic (LQ) model for description of mammalian cell survival curves to evaluate radiosensitization in dependence on dose.

Methods And Materials: Data on clonogenic assays concerning the combined effects of radiation with hyperthermia and halogenated-pyrimidines, were analyzed according to the LQ formula for cell survival: S(D)/S(0) = exp-(αD+βD(2)). Effects of these agents on the linear parameter α and the quadratic parameter β are compared to evaluate differences depending on the applied dose, and the possible relations to mechanisms of radiosensitization.

Quantifying the combined effect of radiation therapy and hyperthermia in terms of equivalent dose distributions.

Purpose: To develop a method to quantify the therapeutic effect of radiosensitization by hyperthermia; to this end, a numerical method was proposed to convert radiation therapy dose distributions with hyperthermia to equivalent dose distributions without hyperthermia.

Methods And Materials: Clinical intensity modulated radiation therapy plans were created for 15 prostate cancer cases. To simulate a clinically relevant heterogeneous temperature distribution, hyperthermia treatment planning was performed for heating with the AMC-8 system.