The goal of this study was to determine the critical ion-radiation conditions under which heavy ion beams can induce DNA double-strand breaks. Helium, nitrogen and argon-ion beams in the energy range of 20 eV to 2 keV were used to irradiate naked DNA plasmid pGFP to fluences of 1, 2 and 4 × 10 ions/cm. The topological forms of DNA were subsequently analyzed using gel electrophoresis. The DNA forms were changed from the original supercoiled to damaged relaxed and linear forms, depending on the ion mass, energy, fluence and inertia. We found ion energy and fluence thresholds above which direct double-strand breaks can occur. The threshold is discussed in terms of the areal ion-energy density and the cross-section.
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http://dx.doi.org/10.1667/RR14721.1 | DOI Listing |
Int J Mol Sci
December 2024
Bayer AG, Research & Development, Pharmaceuticals, 13353 Berlin, Germany.
Despite treatment, prostate cancer commonly progresses into castration-resistant prostate cancer (CRPC), which remains largely incurable, requiring the development of new interventions. Darolutamide is an orally administered second-generation androgen receptor inhibitor indicated for patients with non-metastatic CRPC or metastatic hormone-sensitive prostate cancer. Here, we evaluated the effect of androgen receptor (AR) inhibition by darolutamide in combination with DNA double-strand-break-inducing targeted radium-223 alpha therapy in vitro and in an intratibial LNCaP xenograft model mimicking prostate cancer metastasized to bone.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20057, USA.
DNA repair involves various intricate pathways that work together to maintain genome integrity. XPF (ERCC4) is a structural endonuclease that forms a heterodimer with ERCC1 that is critical in both single-strand break repair (SSBR) and double-strand break repair (DSBR). Although the mechanistic function of ERCC1/XPF has been established in nucleotide excision repair (NER), its role in long-patch base excision repair (BER) has recently been discovered through the 5'-Gap pathway.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Immunology and Molecular Oncology Diagnostics, Veneto Institute of Oncology IOV-IRCCS, 35128 Padua, Italy.
Increased expression of branched-chain amino acid (BCAA) transaminase 1 (BCAT1) often correlates with tumor aggressiveness and drug resistance in cancer. We have recently reported that BCAT1 was overexpressed in a subgroup of T-cell acute lymphoblastic (T-ALL) samples, especially those with NOTCH1 activating mutations. Interestingly, BCAT1-depleted cells showed pronounced sensitivity to DNA-damaging agents such as etoposide; however, how BCAT1 regulates this sensitivity remains uncertain.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Laboratory Animal Resource Center, Transborder Medical Research Center, Institute of Medicine, University of Tsukuba, Tsukuba 305-8575, Japan.
With the groundbreaking advancements in genome editing technologies, particularly CRISPR-Cas9, creating knockout mutants has become highly efficient. However, the CRISPR-Cas9 system introduces DNA double-strand breaks, increasing the risk of chromosomal rearrangements and posing a major obstacle to simultaneous multiple gene knockout. Base-editing systems, such as Target-AID, are safe alternatives for precise base modifications without requiring DNA double-strand breaks, serving as promising solutions for existing challenges.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
College of Life Sciences, Hebei University, Baoding 071002, China.
Bovine herpesvirus 1 (BoHV-1) productive infection induces the generation of DNA double-strand breaks (DSBs), which may consequently lead to cell apoptosis. In response to DSBs, the DNA damage repair-related protein 53BP1 is recruited to the sites of DSBs, leading to the formation of 53BP1foci, which are crucial for the repair of damaged DNA and maintaining genomic integrity by repairing DSBs. In this study, we discovered that HMGA1 may play a significant role in counteracting virus infection-induced DNA damage, as the siRNA-mediated knockdown of HMGA1 protein expression or inhibition of HMGA1 activity by the chemical inhibitor Netropsin uniformly exacerbates the DNA damage induced by BoHV-1 productive infection.
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