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

Abstract

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+βD²). 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.

Results: The values of the linear parameter α, which determines the effectiveness at low doses, are for most cell lines and in most conditions more increased than the values of the parameter β which has a higher contribution at larger radiation doses. These results can be explained by the assumption that the probability of interaction of two DNA double-strand breaks (DSB) produced in close proximity by individual ionizing particles is more enhanced than interaction of DSB produced at larger distances by two separate particles.

Conclusions: The observed differences between values of α and β imply that the radiation enhancement factors are larger at low doses mostly applied in clinical radiotherapy as compared with larger doses as mostly evaluated in experimental studies.

Keywords::

• Linear-quadratic model
• radiosensitization
• hyperthermia
• halogenated pyrimidines

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

The Dutch Cancer Foundation (nos. UVA 2008-4019 and 2012-5540) is acknowledged for financing personnel support.