Bleomycin-induced chromosomal damage and shortening of telomeres in peripheral blood lymphocytes of incident cancer patients
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.
PubMed
29052312
DOI
10.1002/gcc.22508
Knihovny.cz E-resources
- MeSH
- Bleomycin adverse effects pharmacology MeSH
- Chromosome Aberrations drug effects MeSH
- Chromosome Disorders pathology MeSH
- Chromosomes drug effects MeSH
- Adult MeSH
- DNA Breaks, Double-Stranded drug effects MeSH
- Colorectal Neoplasms genetics metabolism MeSH
- Middle Aged MeSH
- Humans MeSH
- Lymphocytes MeSH
- Breast Neoplasms genetics metabolism MeSH
- DNA Repair drug effects MeSH
- Pilot Projects MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Telomere drug effects pathology MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Research Support, U.S. Gov't, Non-P.H.S. MeSH
- Names of Substances
- 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
References provided by Crossref.org
DNA Repair Gene Polymorphisms and Chromosomal Aberrations in Exposed Populations
