Prostaglandins and inhibitors of their synthesis (cyclooxygenase (COX) inhibitors, non-steroidal anti-inflammatory drugs) were shown to play a significant role in the regulation of hematopoiesis. Partly due to their hematopoiesis-modulating effects, both prostaglandins and COX inhibitors were reported to act positively in radiation-exposed mammalian organisms at various pre- and post-irradiation therapeutical settings. Experimental efforts were targeted at finding pharmacological procedures leading to optimization of therapeutical outcomes by minimizing undesirable side effects of the treatments. Progress in these efforts was obtained after discovery of selective inhibitors of inducible selective cyclooxygenase-2 (COX-2) inhibitors. Recent studies have been able to suggest the possibility to find combined therapeutical approaches utilizing joint administration of prostaglandins and inhibitors of their synthesis at optimized timing and dosing of the drugs which could be incorporated into the therapy of patients with acute radiation syndrome.

• Keywords
• acute radiation syndrome, cyclooxygenase, gastrointestinal system, hematopoiesis, inhibitors of prostaglandin synthesis, prostaglandins,
• MeSH
• Acute Radiation Syndrome blood   drug therapy   etiology   metabolism   MeSH
• Cyclooxygenase 1 metabolism   MeSH
• Cyclooxygenase 2 metabolism   MeSH
• Hematopoiesis drug effects   MeSH
• Cyclooxygenase 2 Inhibitors pharmacology   therapeutic use   MeSH
• Humans MeSH
• Metabolic Networks and Pathways drug effects   MeSH
• Disease Models, Animal MeSH
• Prostaglandins biosynthesis   pharmacology   MeSH
• Radiation-Protective Agents pharmacology   therapeutic use   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Names of Substances
• Cyclooxygenase 1 MeSH
• Cyclooxygenase 2 MeSH
• Cyclooxygenase 2 Inhibitors MeSH
• Prostaglandins MeSH
• Radiation-Protective Agents MeSH

From the very beginnings of radiotherapy, a crucial question persists with how to target the radiation effectiveness into the tumor while preserving surrounding tissues as undamaged as possible. One promising approach is to selectively pre-sensitize tumor cells by metallic nanoparticles. However, though the "physics" behind nanoparticle-mediated radio-interaction has been well elaborated, practical applications in medicine remain challenging and often disappointing because of limited knowledge on biological mechanisms leading to cell damage enhancement and eventually cell death. In the present study, we analyzed the influence of different nanoparticle materials (platinum (Pt), and gold (Au)), cancer cell types (HeLa, U87, and SKBr3), and doses (up to 4 Gy) of low-Linear Energy Transfer (LET) ionizing radiation (γ- and X-rays) on the extent, complexity and reparability of radiation-induced γH2AX + 53BP1 foci, the markers of double stand breaks (DSBs). Firstly, we sensitively compared the focus presence in nuclei during a long period of time post-irradiation (24 h) in spatially (three-dimensionally, 3D) fixed cells incubated and non-incubated with Pt nanoparticles by means of high-resolution immunofluorescence confocal microscopy. The data were compared with our preliminary results obtained for Au nanoparticles and recently published results for gadolinium (Gd) nanoparticles of approximately the same size (2⁻3 nm). Next, we introduced a novel super-resolution approach-single molecule localization microscopy (SMLM)-to study the internal structure of the repair foci. In these experiments, 10 nm Au nanoparticles were used that could be also visualized by SMLM. Altogether, the data show that different nanoparticles may or may not enhance radiation damage to DNA, so multi-parameter effects have to be considered to better interpret the radiosensitization. Based on these findings, we discussed on conclusions and contradictions related to the effectiveness and presumptive mechanisms of the cell radiosensitization by nanoparticles. We also demonstrate that SMLM offers new perspectives to study internal structures of repair foci with the goal to better evaluate potential differences in DNA damage patterns.

• Keywords
• DNA damage, DNA double strand breaks (DSBs), DNA repair, DNA repair foci, cancer radiotherapy, damage to lysosomes, metal nanoparticles, single-molecule localization microscopy (SMLM), super-resolution microscopy, tumor cell radiosensitization,
• MeSH
• DNA Breaks, Double-Stranded radiation effects   MeSH
• Gadolinium chemistry   MeSH
• HeLa Cells MeSH
• Microscopy, Confocal MeSH
• Metal Nanoparticles chemistry   therapeutic use   MeSH
• Humans MeSH
• Cell Line, Tumor MeSH
• DNA Damage radiation effects   MeSH
• Gold chemistry   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Gadolinium MeSH
• Gold MeSH