ArticleMolecular medicine (Cambridge, Mass.)2024
Bleomycin induces senescence and repression of DNA repair via downregulation of Rad51.
Article in Molecular medicine (Cambridge, Mass.), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 18 citations in OpenAlex.
- An integrated multi-algorithm analysis to decipher senescence and metabolic characteristics in nucleus pulposus cells during disc degeneration.GeroScience · 2026Article
- Substrate Stiffness and Viscoelasticity Influence Fibroblast Senescence.Journal of biomedical materials research. Part A · 2026Article
- High-Salt Diet-Induced Endothelial Dysfunction Is Mediated by Cellular Senescence.Journal of the American Heart Association · 2026Article
- Targeting the DNA damage repair protein RAD51 alters fibroblast metabolism and enhances apoptosis in pulmonary fibrosis.bioRxiv : the preprint server for biology · 2026Article
- [Mefloquine HCl promotes DNA repair and alleviates radiation-induced lung epithelial cell injury].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2026Article
- ERG phase separation attenuates cellular senescence.iScience · 2026Article
- CHK1 as a Metabolic and Immunological Regulator: Implications for Cancer Therapy.Oncology research · 2026Review
- Hesperetin Alleviates Bleomycin-Induced Pulmonary Fibrosis by Modulating Cellular Senescence and Promoting Impaired Autophagy in a CISD2-Dependent Manner.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Elucidating DNA Damage-Dependent Immune System Activation.International journal of molecular sciences · 2025Review
- Unraveling senescence in cancer: mechanistic complexities and therapeutic opportunities.Molecular biology reports · 2025Review
- Regulation of cellular senescence in tumor progression and therapeutic targeting: mechanisms and pathways.Molecular cancer · 2025Review
- Boanmycin overcomes bortezomib resistance by inducing DNA damage and endoplasmic reticulum functional impairment in multiple myeloma.Biology direct · 2025Article
- The unique Pt(II)-induced nucleolar stress response and its deviation from DNA damage response pathways.The Journal of biological chemistry · 2024Article
- Amodiaquine ameliorates stress-induced premature cellular senescence via promoting SIRT1-mediated HR repair.Cell death discovery · 2024Article
- Review
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundBleomycin, a potent antitumor agent, is limited in clinical use due to the potential for fatal pulmonary toxicity. The accelerated DNA damage and senescence in alveolar epithelial cells (AECs) is considered a key factor in the development of lung pathology. Understanding the mechanisms for bleomycin-induced lung injury is crucial for mitigating its adverse effects.
methodsHuman lung epithelial (A549) cells were exposed to bleomycin and subsequently assessed for cellular senescence, DNA damage, and double-strand break (DSB) repair. The impact of Rad51 overexpression on DSB repair and senescence in AECs was evaluated in vitro. Additionally, bleomycin was intratracheally administered in C57BL/6 mice to establish a pulmonary fibrosis model.
resultsBleomycin exposure induced dose- and time-dependent accumulation of senescence hallmarks and DNA lesions in AECs. These effects are probably due to the inhibition of Rad51 expression, consequently suppressing homologous recombination (HR) repair. Mechanistic studies revealed that bleomycin-mediated transcriptional inhibition of Rad51 might primarily result from E2F1 depletion. Furthermore, the genetic supplement of Rad51 substantially mitigated bleomycin-mediated effects on DSB repair and senescence in AECs. Notably, decreased Rad51 expression was also observed in the bleomycin-induced mouse pulmonary fibrosis model.
conclusionsOur works suggest that the inhibition of Rad51 plays a pivotal role in bleomycin-induced AECs senescence and lung injury, offering potential strategies to alleviate the pulmonary toxicity of bleomycin.
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