We examined the delayed induction of telomere instability in hTERT-immortalized normal human fibroblast (BJ1-hTERT) cells exposed to X-rays. BJ1-hTERT cells were irradiated with 2 Gy of X-rays, and chromosome aberrations were analyzed 24 hours after irradiation and in the surviving cells 14 days after X-ray exposure. We found that the X-ray-surviving cells showed an increased frequency of chromatid gaps and breaks and chromosome fragments compared to the control cells. Furthermore, centromere- and telomere-FISH revealed that the frequency of telomere loss and duplication significantly increased in surviving cells compared to the control level. Because no induction of telomere abnormality was observed in cells 24 hours after irradiation, X-irradiation might not affect telomeres directly, but it specifically induces delayed telomere instability in normal human fibroblast cells.
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http://dx.doi.org/10.1269/jrr.45.105 | DOI Listing |
Biomolecules
November 2024
Molecular Toxicology Group, Department of Biology, University of Konstanz, 78457 Konstanz, Germany.
Chronic stress is associated with a higher risk for carcinogenesis as well as age-related diseases and immune dysfunction. There is evidence showing that psychological stress can contribute to premature immunosenescence. Therefore, the question arose whether chronic exposure to catecholamine could drive immune cells into senescence.
View Article and Find Full Text PDFMol Biol Rep
December 2024
Department of Genetics, Dr. ALM PG Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai, Tamilnadu, 600113, India.
Introduction: The changes in histone modifications are linked to the progression of benign and normal tissue to malignancy. Thus, numerous findings suggest that targeting epigenetic factors might be a focus for anti-cancer treatment. In this study, we tested the hypothesis that telomerase activator might be a potential epigenetic regulator in combatting skin cancer cell proliferation.
View Article and Find Full Text PDFEur J Pharm Sci
December 2024
Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea. Electronic address:
Castrate-resistant prostate cancer (CRPC) is one of the most difficult cancers in men and is characterized by a poor prognosis and a high risk of metastasis. The overexpression of the disruptor of telomeric silencing 1-like (DOT1L), which is a specific methyltransferase for histone H3 at lysine residue 79 (H3K79), has been related to poor outcomes in patients with CRPC. Therefore, targeting DOT1L is considered a potential therapeutic approach to overcome the significant medical challenges of CRPC.
View Article and Find Full Text PDFOpen Biol
December 2024
Department of Oncology, University of Oxford, Oxford OX3 7DQ, UK.
Approximately 10-15% of human cancers are telomerase-negative and maintain their telomeres through a recombination-based process known as the alternative lengthening of telomeres (ALT) pathway. Loss of the alpha-thalassemia/mental retardation, X-linked (ATRX) chromatin remodeller is a common event in ALT-positive cancers, but is generally insufficient to drive ALT induction in isolation. We previously demonstrated that ATRX binds to the MRN complex, which is also known to be important in the ALT pathway, but the molecular basis of this interaction remained elusive.
View Article and Find Full Text PDFAdjuvant therapy with bacteriophage (phage) cocktails in combination with antibiotics is a therapeutic approach currently considered for treatment of infections with encapsulated, biofilm forming, and multidrug-resistant Klebsiella pneumoniae (Kp). Klebsiella phage are highly selective in targeting a bacterial capsule type. Considering the numerous Kp capsule types and other host restriction factors, phage treatment could be facilitated when generating phages with a broad host range.
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