Extrachromosomal DNA can integrate into the genome with no sequence specificity producing an insertional mutation. This process, which is referred to as random integration (RI), requires a double stranded break (DSB) in the genome. Inducing DSBs by various means, including ionizing radiation, increases the frequency of integration. Here we report that non-lethal physiologically relevant doses of ionizing radiation (10-100 mGy), within the range produced by medical imaging equipment, stimulate RI of transfected and viral episomal DNA in human and mouse cells with an extremely high efficiency. Genetic analysis of the stimulated RI (S-RI) revealed that it is distinct from the background RI, requires histone H2AX S139 phosphorylation (γH2AX) and is not reduced by DNA polymerase θ (Polq) inactivation. S-RI efficiency was unaffected by the main DSB repair pathway (homologous recombination and non-homologous end joining) disruptions, but double deficiency in MDC1 and 53BP1 phenocopies γH2AX inactivation. The robust responsiveness of S-RI to physiological amounts of DSBs can be exploited for extremely sensitive, macroscopic and direct detection of DSB-induced mutations, and warrants further exploration in vivo to determine if the phenomenon has implications for radiation risk assessment.
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http://dx.doi.org/10.1371/journal.pgen.1008550 | DOI Listing |
BMC Pharmacol Toxicol
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Biochemistry Department, Faculty of Science, Ain-Shams University, Cairo, Egypt.
Hepatic encephalopathy (HE) is a syndrome that arises from acute or chronic liver failure. This study was devised to assess the impact of a combination of boswellic acid (BA) and low doses of gamma radiation (LDR) on thioacetamide (TAA)-induced HE in an animal model. The effect of daily BA treatment (175 mg/kg body weight, for four weeks) and/or fractionated low-dose γ-radiation (LDR; 0.
View Article and Find Full Text PDFBMC Microbiol
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Department of Microbiology and Immunology, Faculty of Pharmacy, Cairo University, Kasr El-Aini Street, Cairo, 11562, Egypt.
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January 2025
Department of Physics and Astronomy, Aarhus University, Ny Munkegade 120, Aarhus, Midtjylland, 8000, DENMARK.
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View Article and Find Full Text PDFInsights Imaging
January 2025
Department of Radiology, Charité - Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt- Universität zu Berlin, Charitéplatz 1, Berlin, Germany.
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Int J Cell Biol
January 2025
Department of Biotechnology and Plant Breeding, Sari Agricultural Sciences and Natural Resources University (SANRU), Sari, Iran.
Radiation therapy is one of the most effective treatments for approximately 60% of patients with cancer. During radiation exposure, the overproduction of reactive oxygen species (ROS) disrupts the lipid layer of the membrane, leading to subsequent peroxide radical formation. Cimetidine (Cim) and famotidine (Fam) are histamine H2 receptor antagonists (H2 blocker), also known as peptic ulcer drugs, that exert radioprotective effects.
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