Ionizing radiation exposure produces direct or indirect biological effects on genomic DNA. The latter are ionizing radiation mediated by induction of free radicals and oxygen species (ROS). The study was conducted to evaluate the dose-effect/time-effect of antioxidant treatments in reducing the induction of double-strand breaks in human blood lymphocytes. Human peripheral blood samples of 2 mL each from healthy donors were irradiated with 10 mGy after pre-incubation with different antioxidants (β-carotene, vitamin E, vitamin C, N-acetyl L-cysteine). In order to assess their efficiency as prophylactic therapy for irradiation, various concentrations and combinations of antioxidants, as well as different incubation times, have been evaluated. To assess double-strand breaks induced by ionizing radiation, the phosphorylated histone γ-H2AX has been used. A significant reduction (p < 0.001) in double-strand breaks studied with a γ-H2AX assay was observed with N-acetyl L-cysteine with a 1-h incubation time, followed by vitamin C, vitamin E, and β-carotene. The use of antioxidants, especially N-acetyl L-cysteine before irradiation, significantly decreased the occurrence of double-strand breaks, demonstrating the potential radiological protection for exposure to ionizing radiation.
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http://dx.doi.org/10.1097/HP.0000000000001267 | DOI Listing |
Front Oncol
January 2025
Department of Biology, Tufts University, Medford, MA, United States.
REV7, also known as MAD2B, MAD2L2, and FANCV, is a HORMA-domain family protein crucial to multiple genome stability pathways. REV7's canonical role is as a member of polymerase ζ, a specialized translesion synthesis polymerase essential for DNA damage tolerance. REV7 also ensures accurate cell cycle progression and prevents premature mitotic progression by sequestering an anaphase-promoting complex/cyclosome activator.
View Article and Find Full Text PDFBreast Cancer Res
January 2025
Department of Cancer Biology, Wake Forest University School of Medicine, Winston-Salem, NC, 27157, USA.
Obesity is a modifiable risk factor for breast cancer. Yet, how obesity contributes to cancer initiation is not fully understood. The goal of this study was to determine if the body mass index (BMI) and metabolic hallmarks of obesity are related to DNA damage in normal breast tissue.
View Article and Find Full Text PDFBiomedica
December 2024
Servicio de Inmunología y Alergología, Fundación Universitaria Ciencias de la Salud - FUCS, Bogotá, D. C., Colombia.
Cernunnos/XLF deficiency is a rare, severe combined immunodeficiency, inherited in an autosomal recessive pattern (OMIM number: 611290), related to the NHEJ1 gene. This gene participates in the DNA non-homologous end-joining pathway, repairing double-strand breaks in the DNA of mammalian cells. The clinical features include growth retardation, microcephaly, triangle-shaped face, recurrent infections, fibroblast's excessive sensitivity to gamma-ionizing radiation, and hypogammaglobulinemia; also, low counts of subpopulations of B and T lymphocytes, with normal values of natural-killer cells.
View Article and Find Full Text PDFJ Med Chem
January 2025
School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei 110, Taiwan.
Since decades after temozolomide was approved, no effective drugs have been developed. Undoubtedly, blood-brain barrier (BBB) penetration is a severe issue that should be overcome in glioblastoma multiforme (GBM) drug development. In this research, we were inspired by linezolid through structural modification with several bioactive moieties to achieve the desired brain delivery.
View Article and Find Full Text PDFCell Mol Life Sci
January 2025
Experimental Neurosurgery, Department of Neurosurgery, Neuroscience Center, Goethe University Hospital, Goethe University Frankfurt, 60528, Frankfurt am Main, Germany.
Glioblastoma (GBM), the most malignant primary brain tumor in adults, has poor prognosis irrespective of therapeutic advances due to its radio-resistance and infiltrative growth into brain tissue. The present study assessed functions and putative druggability of BRCA1-associated ATM activator 1 (BRAT1) as a crucial factor driving key aspects of GBM, including enhanced DNA damage response and tumor migration. By a stable depletion of BRAT1 in GBM and glioma stem-like (GSC) cell lines, we observed a delay in DNA double-strand break repair and increased sensitivity to radiation treatment, corroborated by in vitro and in vivo studies demonstrating impaired tumor growth and invasion.
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