Effect of DNA and Ions – Radiation Biology

Effect of DNA and Ions Radiation Biology
Effect of DNA and Ions Radiation Biology - In simulations where a DNA molecule is "dissolved" into its constituent parts, water (light blue spheres), nucleobases (dark blue spheres), and sugar-phosphate side chains (magenta spheres), an incoming proton (H+) transfers to the molecule It turns out that the energy depends on the location of the impact zone. When a proton hits a sugar-phosphate side chain (red), two to three times more energy is transferred than when it hits a nucleobase (turquoise). Therefore, radiation hitting a side chain is more likely to damage it.

The causes of damage during proton radiotherapy have been clarified by research on the electron excitation response of DNA to proton radiation. According to studies on the effects of ionizing radiation on human health in the field of radiation biology, deoxyribonucleic acid (DNA) is the main target of the harmful effects of radiation. Ionizing radiation can cause significant localized energy accumulation in DNA to cause double helix breaks, which can cause mutations, chromosomal abnormalities, and changes in gene expression. To create radiation treatments and improve radiation protection measures, it is crucial to understand the mechanisms underlying these interactions.

Christopher Shepard of the University of North Carolina at Chapel Hill and his colleagues are using powerful computer simulations to show exactly which part of the DNA molecule absorbs harmful energies when exposed to charged particle radiation. His research may one day contribute to reducing the long-term radiation effects of cancer treatments and human spaceflight.

The interaction of radiation with the electrical structure of DNA requires a complex process. The precise dynamics of these interactions at the atomic level are not captured by the computer models currently used in radiobiology and therapeutic radiotherapy. Instead, these models determine whether a radiation particle, such as a photon or ion, that crosses the cell volume, will transmit enough energy to break one or both of the DNA strands using geometric sections. The models only give the probability that a population of cells will stop reproducing after receiving a certain dose of radiation, without describing interactions at the atomic level.

Ionizing radiation, which has the potential to inactivate cells, can be used to stop tumor growth. In reality, radiation is still among the most commonly used cancer treatments. However, when used to treat cancer, the treatment can have adverse effects on healthy tissues. High-energy photons lose energy rapidly after they enter the body in gamma-ray and x-ray therapy. On the other hand, the charged particles used in heavy ion radiotherapy lose most of their energy near the end of their travel distance. Especially for fast moving particles, this high energy loss at a very short distance causes a significant increase in the energy accumulated in a restricted volume.

The ability to precisely target a tumor form and depth with a charged particle beam allows radiotherapists to reduce damage to healthy tissue beyond the tumor while sparing healthy tissue in front of the tumor. Due to its selectivity, heavy ion radiation is a state-of-the-art therapeutic approach that can cure malignancies that are no longer considered incurable with conventional treatments.

Coulomb interactions between electron orbitals are responsible for most of the energy that a charged particle transfers to a medium. The term "radiation arresting power" refers to a material's capacity to delay or stop charged particles such as electrons or ions as they pass through it. The average energy required to ionize an atom or molecule in a medium is often used to measure this capacity.

The effectiveness of radiation therapy should be evaluated by measuring the stopping power of a substance. Stopping power is typically expressed in terms of energy expended per millimeter of motion for biological tissues. Because a DNA molecule has an average width of 2 nm, it is not currently possible to measure the stopping power on the DNA scale.

Shepard and colleagues measured the energy transfer from high-energy protons to dissolved DNA, or a DNA solution split into sugar-phosphate side chains and nucleobase backbone components, using large-scale computational simulation on supercomputers. They evaluated the molecular complexity of the DNA system using time-dependent density-functional theory (DFT). DFT is a computational technique used to investigate the electronic composition of solids, molecules and atoms. It is based on the idea that a single function characterizing the electron density of the system can predict the properties of a multi-electron system.

Instead of solving the Schrödinger equation for each electron in the system, DFT uses a set of assumptions to account for interactions between electrons, making it an effective method for determining the electronic structure of large systems. Calculation of the electrical structure of complex systems that were impossible to study using conventional techniques is now possible thanks to approximations.

The researchers used simulations to describe the overall energy of the dissolved DNA system as a mathematical function dependent on electron density. The wave function of the system, which describes the probability of finding an electron with a certain spin at a given position, can be used to calculate the electron density. Using this method, they discovered that electron displacement is highly localized throughout the proton's journey and is much higher in orbitals closer to the phosphate chains. More displacement means that the sugar-phosphate backbone of DNA absorbs more energy than nucleobases.

The simulations cast doubt on the popular belief that stopping power is inversely proportional to the numerical density of holes produced in the medium. In light of their findings, Shepard and colleagues argue that the stopping capacity of the dissolved DNA medium also depends on the energy of the holes created. According to their findings, the sugar-phosphate backbone exhibits a higher electron hole generation frequency, which can result in the generation of seriously harmful free radicals. Aqueous atoms or molecules that have an unpaired valence electron and are therefore highly reactive with the local environment are known as free radicals. As a result of the radicals reacting with the sugar-phosphate backbone, one or more of the DNA strands may eventually break.

This work demonstrates the value and power of high-performance, multi-core computers for investigating complex interaction dynamics that are otherwise difficult to reproduce in a lab setting. The findings help bridge the knowledge gap between radiobiology and charged particle transport physics by identifying where charged particles concentrate most of their energy within a DNA molecule. However, accepting the results of the study should be done with some caution until extensive empirical evidence is available to support the researchers' hypotheses. The efficacy of therapeutic ionizing radiation can be improved with a better understanding of the mechanisms underlying DNA damage. They can also create defenses, such as new drugs, against the harmful effects of ionizing radiation on healthy cells.

Source: physics.aps.org/articles/v16/41

Günceleme: 14/03/2023 13:13

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