Modifying Effect of Different Forms of Lipid A on the Induction of DNA Double-Strand Breaks in Mice Hippocampal Cells After Exposure to Ionizing Radiation of Different Quality in Vitro

摘要

The search for new techniques and preparations modifying the radio sensitivity of different organisms' cells by immune system activity modulation is of immediate interest to radiation biology. A promising approach is to study the modifying influence of lipopolysaccharides and their derivatives that are widely used in biomedical research and pharmacology on radiation-induced effects. Lipid A is one of such agents; it shows high biological activity at low concentrations and can be an immune response modulator. In this work, the modifying effect of different modifications of lipid A - diphosphoryl lipid A (DLA) and monophosphoryl lipid A (MLA) - on the induction of DNA double-strand breaks (DSB) in mice hippocampal cells after in vitro exposure to ~(60)Co γ-rays and accelerated ~(15)N ions has been studied. It has been found that the DNA DSB yield is linear for both types of radiation. The highest DSB yield was observed after accelerated ~(15)N ion exposure. For both types of radiation, the studied agents have different influence on cells' radio sensitivity: DLA has a radiosensitizing effect; MLA, radioprotective. It can be suggested that MLA's radioprotective properties are realized due to signal pathway activation involving toll-like receptors (TLR4). The repair kinetics of DNA DSB in mice hippocampal cells after in vitro exposure to ~(60)Co γ-rays and accelerated ~(15)N ions at a dose of 5 Gy under normal conditions has been studied. It has been found that DNA DSB repair kinetics has an exponential character, and repair is practically complete after 6 h of post-irradiation incubation for both types of ionizing radiation.