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Biological Effects and Medical Treatment
Published in Alan Perkins, Life and Death Rays, 2021
Indirect effects result from much more common products of the ionisation trail from the ray or particle and can induce chemical changes in the molecules contained in living cells. All biological systems are predominantly made up of water and the radiation-induced splitting of water molecules (radiolysis) can start the process of causing biological damage. This occurs in four stages, three of which take place quickly and one much more slowly. The sequence of events resulting in radiation damage are summarised in Table 11.3.
Radioimmunotherapy of Hematological Malignancies
Published in Gertjan J. L. Kaspers, Bertrand Coiffier, Michael C. Heinrich, Elihu Estey, Innovative Leukemia and Lymphoma Therapy, 2019
90Y offers a number of theoretical advantages over 131I, although the radioisotopes have not been directly compared by labeling the same mAbs described in this chapter with either isotope. 90Y is a pure β-emitter that produces higher energy radiation (2.3 MeV vs. 0.6 MeV) at a longer path length than 131I (5.3 mm vs. 0.8 mm). Radiolysis induces cellular damage in both the targeted lymphoma cells and neighboring cells. The increased path length would be expected to enhance the “cross fire” effect and could, therefore, be potentially advantageous in treating bulky, poorly vascularized tumors with heterogeneous antigen expression (4). This longer path length is likely, however, to increase the normal tissue dose when targeting microscopic disease for which the shorter β-particle path length of 131I may be preferable.
Autoradiography
Published in Howard J. Glenn, Lelio G. Colombetti, Biologic Applications of Radiotracers, 2019
Sven Ullberg, Bengt Larsson, Hans Tjälve
Another problem is self-decomposition of radiochemicals (radiolysis),3 especially when compounds with high specific activities are concerned. The radiochemical purity of a substance therefore ought to be checked routinely before use. Different modes of radiolysis can be discerned: natural isotopic decay, direct interaction of the radioactive emission with molecules of the compound, and the secondary effects of radioproduced excited-state species from the environment (e.g., the solvent). Severe problems exist in the storage of substances with a high specific activity, e.g., tritium-labeled compounds. Radiolysis may be decreased by the dispersion of the labeled compound in a suitable medium, usually a solvent. It is also advisable to store the radiochemicals at their correct pH for maximum chemical stability. As a general rule, compounds (particularly organic molecules because of their thermodynamic instability) are best kept at low temperatures, especially when they are dissolved and a radical scavenger is present in the solution.
Hematopoietic protection and mechanisms of ferrostatin-1 on hematopoietic acute radiation syndrome of mice
Published in International Journal of Radiation Biology, 2021
Xiaohong Zhang, Mengxin Tian, Xin Li, Chunyan Zheng, Ailian Wang, Jundong Feng, Xiaodan Hu, Shuquan Chang, Haiqian Zhang
The indirect effect of ionizing radiation arising from water radiolysis products (hydroxyl radicals, hydrogen radicals, and hydrated electrons) induces the most of ionizing radiation-induced damage in organisms (Miao et al. 2014). Therefore, both ionizing radiation-induced injuries and ferroptosis are ROS-related. Several research groups have reported that radiation induces ferroptosis in cancer cells (Lei et al. 2020; Ye et al. 2020). More importantly, Thermozier et al. (2020) found that baicalein, an anti-ferroptosis drug, synergistically improves the survival rate of hARS-mice with anti-apoptosis and anti-necroptosis drugs. These indicate that ionizing radiation is an exogenous inducer of ferroptosis (Stockwell and Jiang 2020), whereby targeting ferroptosis mitigates radiation damage. At the same time, our group demonstrated that the intraperitoneal injection of ferrostatin-1 is able to effectively increase the survival rate of hARS-mice to 60% for 150 days (Zhang et al. 2020). However, the mechanism by which ferrostatin-1 mitigates radiation-induced ferroptosis, and subsequent hARS, remains unknown.
Role of DNA damage and repair in radiation cancer therapy: a current update and a look to the future
Published in International Journal of Radiation Biology, 2020
Jingya Liu, Kun Bi, Run Yang, Hongxia Li, Zacharenia Nikitaki, Li Chang
Radiation indirect action refers to the biological damage caused by the chemical reaction of important organic molecules of the cell with active free radicals, formed during the radiolysis of water, that is, the interaction of radiation with atoms of water molecules. As known, the term free radical refers to a free atom, molecule or to a group of atoms, which carries an unpaired electron and it is therefore characterized by increased activity whether or not it is electrically neutral or charged (Dertinger and Jung 1970). The free hydrogen and hydroxyl radicals, the hydrogen cations and the hydrated electrons produced can then -through their dissociation participate in dozens of reactions with each other or with other molecules of the system- trigger a cascade of radicals and oxidations. In this scenario, the oxidative character of IR is predominant. The effect of radiolysis of water by exposure of the cytoplasm to IR is the oxidation of various small molecules and macromolecules. Oxidations of inorganic substances dissolved in the form of ions in the cytoplasm are of no biological significance. However, oxidation of organic compounds is important as it corresponds to the direct action of radiation, leading to polymerizations or de-polymerizations accompanied by a change in physical and chemical properties (Ide et al. 1994; Azzam et al. 2012).
The sequence preference of gamma radiation-induced DNA damage as determined by a polymerase stop assay
Published in International Journal of Radiation Biology, 2019
Megan E. Hardie, Vincent Murray
A substantial proportion of IR-induced DNA damage occurs due to the radiolysis of water molecules. Radiolysis produces reactive oxygen species, including hydroxyl radicals, hydrogen peroxide, superoxide radicals, as well as hydrogen radicals, and solvated electrons (von Sonntag 2006, p. 211–482). Hydroxyl radicals are highly reactive, and readily interact with a variety of biological molecules. They trigger the major indirect radiation damage to DNA through a variety of lesions including base damage, SSBs and DSBs (Prise et al. 1999; Milligan et al. 2000; von Sonntag 2006, p. 211–482). Superoxide radicals and hydrogen peroxide do not react with most biological species (Dizdaroglu and Jaruga 2012). If the unstable solvated electron survives long enough to interact with DNA, the only interaction is with the bases to induce base damage (Holley and Chatterjee 1996).