Bleomycin‐induced chromosomal damage and shortening of telomeres in peripheral blood lymphocytes of incident cancer patients
| Autor: | Sivaramakrishna Rachakonda, Michal Kroupa, Ludmila Vodickova, Markéta Urbanová, Zdenka Polivkova, Tomas Buchler, Katerina Jiraskova, Pavel Vodicka, Sona Vodenkova, Kari Hemminki, Michaela Schneiderova, Rajesh Kumar |
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| Rok vydání: | 2017 |
| Předmět: |
Adult
Male 0301 basic medicine Cancer Research DNA Repair Colorectal cancer DNA repair Breast Neoplasms Chromosome Disorders Pilot Projects Mutagen Biology medicine.disease_cause Bleomycin Chromosomes 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Genetics medicine Humans DNA Breaks Double-Stranded Lymphocytes Aged Aged 80 and over Chromosome Aberrations Cancer Middle Aged Telomere medicine.disease 030104 developmental biology chemistry 030220 oncology & carcinogenesis Cancer research Female Chromatid Colorectal Neoplasms Carcinogenesis |
| Zdroj: | Genes, Chromosomes and Cancer. 57:61-69 |
| ISSN: | 1098-2264 1045-2257 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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