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Radiosensitization with Chemotherapeutic Agents and Hyperthermia: Effects on Linear-quadratic Parameters of Radiation Cell Survival Curves

Abstract

Nicolaas A.P. Franken, Suzanne Hovingh, Hans Rodermond, Lukas Stalpers, Gerrit W. Barendsen and Johannes Crezee

The radio-sensitizing effects of several chemotherapeutic agents and hyperthermia have been investigated in several animal and human cell culture systems. Cells are first treated with Cisplatin, Gemcitabine, Halogenated pyrimidines or hyperthermia and thereafter irradiated with different dose of radiation up to 8 Gy. After treatment the clonogenic survival was determined and from the survival curves the values of the linear and quadratic parameters were determined using the formula S(D)/S(O)= exp-(αD+βD2).

An increase in the value of the linear parameter, α, was observed in most cases, which corresponds to an enhanced (potentially) direct lethal damage (PLD) at low doses. The quadratic parameter β, which is assumed to depend on the interaction of sublethal lesions (SLD), was rarely affected. Furthermore, it appeared that more radioresistant cell lines were more sensitised than the radiosensitive lines. Furthermore it can be concluded that radiosensitization is also dependent on cell cycle stage like plateau or exponentially growing phase or post treatment plating conditions.

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