Abstract
Experimental evidence indicates that cells under irradiation induce in the neighbour non- irradiated cells the same biological effects affecting the irradiated ones. This is the so called bystander effect. Up to now in the scientific literature this kind of effect does not appear to be fully understood, even if several experiments show evidence of its existence. It would be reasonable that bystander effect takes place by means of paracrine chemical transmission mediators that would be broadcasted by the damaged cells to the surrounding cells. Furthermore a subset of a special class of signaling proteins, namely the cytokines, are probably the very ones involved in such signaling phenomenon. Among them, Tumor Necrosis Factor (TNF) is a particularly relevant protein belonging to the class of cytokines, because it is known to contribute to mediate various relevant cell functions, like apoptosis, the programmed cell death. As a molecule, TNF is quite interesting, because it can issue two opposite signals through different intracellular molecular signaling chains. One signal induces apoptosis, while the other is opposite, inducing the cell resistance to apoptic signals. The crucial point is thus to understand what makes each of such two signals masking the other. Thus a mathematical model related to the TNF signaling pathway is of interest, paying special attention to the study of the TNF reception mechanisms by cells that are not passed through by the radiation beam. In this work we present a new mathematical model of cellular apoptosis - mediated by TNF - and its validation based on data existent in literature. The model that we present will result to be a stable model with respect to large variation of the parameters and simplified with respect to other models already existent.
Highlights
In Radiobiology the bystander effect is the phenomenon inducing unirradiated cells to exhibit irradiated effects because of signals received from nearby irradiated cells
The bystander effect have many consequences such as genomic instability pertaining the nucleus, and Apoptosis pertaining the cytoplasm, that is the object of this paper
One of the most accredited hypothesis is that the bystander effect takes place by means of a special class of signaling proteins, namely the cytokines: among them, Tumor Necrosis Factor (TNF) seems to be the most relevant protein because it is known to contribute to mediate various cell functions, like cell survival and proliferation, or apoptosis [3,4,5,6]
Summary
In Radiobiology (field of science that studies the biological effect of ionizing and non-ionizing radiation on cells) the bystander effect is the phenomenon inducing unirradiated cells to exhibit irradiated effects because of signals received from nearby irradiated cells. One of the most representative experiments sounds as follows: cell population becomes radiated, its culture medium is conveyed to another environment where non-radiated cells live; afterwards the non-radiated cells show to suffer the same types of effect as the radiated cells Such effect is detected even if the power of the ionizing radiation is small. The action mechanism of the bystander effect is intended to be the diffusion of one or more factors from the irradiated cells to the surrounding nonirradiated ones Such factors bound (at the membrane level) with the conjugate receptors of the target cells. Such a signaling triggers a series of different phenomena among whom genomic instability, and especially Apoptosis are of our main interest.
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