Ataxia Telengectesia Protein Influences Bleomycin-Induced DNA Damage in Human Fibroblast Cells

Human cancer is caused mainly by exposure to genotoxic chemicals; therefore, cellular defence mechanisms against genotoxic stress are crucial. Genetic factors are essential to maintaining genome stability and play a vital role in overcoming this by repairing the genome damage caused by any agent in...

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Bibliographic Details
Published in:Cell biochemistry and biophysics 2024-06, Vol.82 (2), p.1235-1242
Main Authors: Tamizh Selvan, G., Venkatachalam, P.
Format: Article
Language:English
Subjects:
Ataxia
Ataxia telangiectasia
Biochemistry
Biological and Medical Physics
Biomedical and Life Sciences
Biophysics
Biotechnology
Bleomycin
Cancer
Cell Biology
Chemical damage
Chromosomes
Damage prevention
Deoxyribonucleic acid
DNA
DNA damage
DNA repair
Fibroblasts
Genetic factors
Genomes
Genomic instability
Genotoxic chemicals
Genotoxicity
Life Sciences
Mutagens
Original Paper
Pharmacology/Toxicology
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Summary:Human cancer is caused mainly by exposure to genotoxic chemicals; therefore, cellular defence mechanisms against genotoxic stress are crucial. Genetic factors are essential to maintaining genome stability and play a vital role in overcoming this by repairing the genome damage caused by any agent in order to prevent chromosomal instability. To examine the influence of the genetic makeup in specific ataxia-telangiectasia (ATM), we have examined non-cancerous fibroblast cell lines (HLF, AG1522 and L6) and cells with ATM mutated deficiency (GM4405). Cell lines were exposed in vitro to bleomycin (0, 40 and 80 µg/mL). The induced DNA damages were measured using endpoints including the micronucleus assay (MN) to measure chromosome damage and gamma-H2AX (γ-H2AX) assay to measure DNA damage/repair foci formation. An increase in DNA damage were observed in bleomycin-treated cells compared to unexposed controls ( p   HLF > AG1522 > L6 for MN frequency and HLF > AG1522 > GM4405 > L6 for γ-H2AX foci. These findings suggest that the genetic makeup of the cellular genome would play an essential role in repairing bleomycin-induced DNA damage. Signalling of DNA damage, and the genes responsible for the repair process, could contribute to the differential susceptibility of different tissues to carcinomas induced by environmental mutagens.
ISSN:1085-9195
1559-0283
1559-0283
DOI:10.1007/s12013-024-01275-z