The experiment TENORE is aimed to contribute to the comprehension of how, in a multicellular environment, the molecular and cellular responses to ionizing radiation are integrated to give a response at the organism level. The approach is to consider the radiation induced effect as the result of a perturbative process and of the following response of the biological system; this response is integrated at a multi-scale (molecular, cellular, over-cellular, organ and organism) level.
The main starting point for the analysis of the biological response is represented by the study of the track structure and, more generally, by the ionizing radiation quality. In fact, the initial damage can be both quantitatively and qualitatively different (especially at low doses and at low dose rates), with consequently different evolutions of the damage and of the biological response.
It must be underlined that in the last two decades we have witnessed an important perspective change in radiation biology: from a DNA-centric point of view we have shifted to a more complex approach, in which important roles are played also by “complementary” targets, that determine very diverse and system dependent cellular responses. The role of DNA is still fundamental, but it is no more exclusive, since it must be integrated in a “sensor” system of the radiation induced cellular modifications. Important experimental and theoretical works are studying biological effects in cells that are not directly hit by radiation, but that are in the vicinities of irradiated cells (bystander effect). The cellular signalling is gaining importance as a fundamental aspect of the responses to radiation (relevant for the radiation effects on tissues and organs), in which the cells do not respond as isolated elements, but as integrated systems in mutual communication through the transmission of biochemical signals. An adaptive response (resistance to radiation, induced by the exposition to a low dose of ionizing radiation, with respect to a following irradiation) represents a further very interesting phenomenon, able to modulate the response of the biological system to radiation.
In this framework, the general objective of the experiment TENORE is to study, with an integrated theoretical and experimental approach, the cellular responses induced by the exposition to ionizing radiation and the cellular mechanisms correlated to such responses, in relation to the radiation quality. To such purpose the cellular response will be studied at different levels: the induction of DNA damage and its consequent repair, the clonogenic cell death, the induction of differentiation, the modulation of lipidic and glucidic metabolism, the response to oxidative stress, the modulation of the intra, inter and extra cellular communication. The main experimental models will be cultured cells, but, since the responses to radiation (at molecular and cellular level) are strongly influenced from the organizational level of the biological system (isolated cells, cellular culture/co-culture, tissue, organ, organism) in the second part of the experiment there will be feasibility studies of threedimensional skin systems in vitro. The experience acquired by our groups on the development of (stochastic and not) models, and of simulation techniques of track structure, will furthermore provide a strong support for the validation of the relevant aspects of the quality of the different radiations used in the project.
Globally, the projects aims to contribute, with a multidisciplinar and integrated approach at theoretical/modelling and experimental level, to the identification of the physical mechanisms and of the radiation biology responses that can play a meaningful role in the induction of tumours and of other biological events that are important at system level.