2023-08-08 15:11:43
We do not see them, but more often than we imagine we are exposed to ionizing radiation: when we sunbathe or when we undergo diagnostic tests with X-rays. Or again if we are on board an intercontinental airliner, which reaches 10 thousand meters of altitude. This type of radiation is potentially dangerous for DNA because it can damage it, break its structure or modify it, up to causing a tumor. Now, researchers from the Physics Department of the University of Trento have revealed, through simulations, the link between the impact of radiation on DNA and the time in which the damaged molecule breaks down irreversibly, opening up new perspectives in the cancer cure.
The group of scholars formed by Manuel Micheloni, Lorenzo Petrolli, Gianluca Lattanzi, and led by Raffaello Potestio has in fact calculated the average time between the ionizing radiation and the breakage of the filament. And he found that the more the distance between the damaged areas of the DNA increases, the longer the structure stays together. Consequently, the time available to the cell to repair it increases. The researchers have created a double-stranded DNA sequence on the computer, like in a sort of video game. After it was hit by the radiation, they observed its behavior. One of the most dangerous effects is the breakage of the DNA known as double-strand break or the interruption of the structural and chemical continuity of the DNA skeleton in the two complementary strands.
This type of injury can trigger harmful consequences at the cellular level. Scholars have understood that the break does not occur immediately and the time it takes for the chain to separate grows exponentially with the distance between the cuts in the DNA. The authors of the work have succeeded in reconstructing the law of the average breaking time with the distance between the cuts. “This information is crucial – underlines Raffaello Potestio – because it probably impacts on the effectiveness of the DNA repair processes”. The cell has a complex enzymatic system of control and ‘maintenance’ of the DNA, which is triggered when it receives signals of injury. This mechanism, however, does not start immediately after the damage, and a delay in this operation can affect the normal functioning of the cell itself.
The sequence modification may not have an impact if it occurs through one or more synonymous mutations, which give rise to the synthesis of the same protein. However, if there are substantial changes in the DNA sequence or errors in the repair procedure, at best the cell commits suicide (technically it ‘goes into apoptosis’), because it realizes that the sequence is wrong or irreparably damaged. In the worst case scenario, however, the cell reconstitutes the integrity of the DNA chain but accumulating mutations or alterations of the nucleotide sequence that could give rise to dysfunctional behavior, which produces genetic modifications, chromosomal mutations or the onset of cancer.
The work – the scholars are convinced – is potentially of great importance in the radiobiological context and represents a first step towards possible developments in the medical field, in therapeutic and preventive practice. A peculiarity of this study is in fact the use of numerical simulation techniques that could be reproduced experimentally: the transfer from the computer to laboratory practice is one of the researchers’ objectives. Understanding what happens when DNA is hit by radiation opens up the long-term perspective of working on new and increasingly precise intervention techniques with radiotherapy.
“The dual and complementary purpose downstream of these studies – underlines Potestio – is on the one hand to understand the mechanisms that lead to cellular damage to prevent or limit them, and on the other to find the best way to create the greatest possible damage. This is important , for example, in the field of proton therapy, which uses ionizing radiation, specifically protons, to locally hit cells that are already cancerous and kill them.The context of radiotherapy – continues the teacher – brings with it a whole series of deeper issues that concern, for example, the precise localization of the radiation deposited in the tumor tissues, in order to prevent the rays from hitting healthy cells which in turn could ‘go crazy’.The better we will understand what happens following the irradiation and the breaking of the DNA, the more we will have arrows to our bow to be able to develop other intervention techniques and mitigate their side effects”, concludes Potestio.
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