Bleomycin-induced chromosomal damage and shortening of telomeres in peripheral blood lymphocytes of incident cancer patients
Jazyk angličtina Země Spojené státy americké Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem, Research Support, U.S. Gov't, Non-P.H.S.
PubMed
29052312
DOI
10.1002/gcc.22508
Knihovny.cz E-zdroje
- MeSH
- bleomycin škodlivé účinky farmakologie MeSH
- chromozomální aberace účinky léků MeSH
- chromozomální poruchy patologie MeSH
- chromozomy účinky léků MeSH
- dospělí MeSH
- dvouřetězcové zlomy DNA účinky léků MeSH
- kolorektální nádory genetika metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- lymfocyty MeSH
- nádory prsu genetika metabolismus MeSH
- oprava DNA účinky léků MeSH
- pilotní projekty MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- telomery účinky léků patologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, U.S. Gov't, Non-P.H.S. MeSH
- Názvy látek
- bleomycin MeSH
Disruption of genomic integrity due to deficient DNA repair capacity and telomere shortening constitute hallmarks of malignant diseases. Incomplete or deficient repair of DNA double-strand breaks (DSB) is manifested by chromosomal aberrations and their frequency reflects inter-individual differences of response to exposure to mutagenic compounds. In this study, we investigated chromosomal integrity in peripheral blood lymphocytes (PBL) from newly diagnosed cancer patients, including 47 breast (BC) and 44 colorectal cancer (CRC) patients and 90 matched healthy controls. Mutagen sensitivity was evaluated by measuring chromatid breaks (CTAs) induced by bleomycin and supplemented by the chemiluminescent measurement of γ-H2AX phosphorylation in 19 cancer patients (11 BC, 8 CRC). Relative telomere length (RTL) was determined in 22 BC, 32 CRC, and 64 controls. We observed statistically significant increased level of CTAs (P = .03) and increased percentage of aberrant cells (ACs) with CTAs (P = .05) in CRC patients compared with controls after bleomycin treatment. No differences were observed between BC cases and corresponding controls. CRC and BC patients with shorter RTL (below median) exhibited significantly higher amount of ACs (P = .02), CTAs (P = .02), and cells with high frequency of CTAs (≥12 CTAs/PBL; P = .03) after bleomycin treatment. No such associations were observed in healthy controls. γ-H2AX phosphorylation after bleomycin treatment in PBL did not differ between CRC and BC patients. Our results suggest that altered DSB repair measured by sensitivity towards mutagen in PBL occurs particularly in CRC carcinogenesis. Irrespective of cancer type, telomere shortening may be associated with a decreased capacity to repair DSB.
Department of Surgery General University Hospital Prague Prague 12800 Czech Republic
Division of Molecular Genetic Epidemiology German Cancer Research Center Heidelberg 69120 Germany
Faculty of Medicine and Biomedical Center in Pilsen Charles University Pilsen 30605 Czech Republic
Citace poskytuje Crossref.org
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