Adaptive response: modelling and experimental studies

Abstract

Adaptive response (AR) is a term that has been generally accepted to describe the ability of a low 'priming' radiation dose to decrease the cell response to a subsequent higher 'challenging' dose. The main proposed mechanisms to explain AR are: increased efficiency of DNA repair and induction of antioxidant enzymes. A model that considers a modulation of the efficiency of DNA repair activity and of the level of antioxidant enzymes, starting from the framework of a lethal-potentially lethal (LPL) model is proposed. The LPL model has been extended with the inclusion of the dynamic variables representing the efficiency of repair, the levels of radiation induced radicals and of antioxidant enzymes. The model used here is able to describe the protective effect of a priming dose. Moreover, in agreement with the data in the literature, the simulations show that the AR happens in given priming dose and priming dose-rate ranges only, and requires at least 4 h to develop. In order to get more insights into the role of cell-cell communication as factors affecting the AR, experimental studies were planned using sparse or confluent AG1522 cell monolayer. The results obtained after gamma irradiation suggest that cell density is a crucial factor for observing an AR.