title: Analysis of telomere damage by fluorescence in situ hybridisation on micronuclei in lymphocytes of breast carcinoma patients after radiotherapy.
abstract: Radiotherapy has become an indispensable tool in the effective management of most of the cancers. There have been efforts earlier to study the differential radio-sensitivity patterns in patients undergoing radiation treatment to correlate with treatment induced complications such as tissue injury, cell death, and chromosomal aberration frequencies etc. The present study is an attempt to correlate the radiation-induced damage in the peripheral blood lymphocytes (PBLs) of breast cancer patients with the frequency of telomere mediated chromosomal damage. Blood samples from 55 patients with (Gr-II and Gr-III) CA-breast were obtained pre- and post-radiotherapy. The patients were treated with external beam radiotherapy of 50.4 Gy over a period of 6 weeks. Chromosome damage was measured by analysing micronucleus (MN) frequency in PBLs. The MN-frequency of the irradiated patients increased significantly compared to the patients being self-controls. The micronuclei were hybridized with telomere probes to study the extent of telomere damage. The fluorescence signals of the telomere regions in the first generation of the binucleated cells were significantly higher in the post-radiotherapy patients. There was also significant correlation observed in the patients with higher-grade tumours. Inter-individual variability was observed in the radiation-induced MN frequency in lymphocytes of patients after six weeks of radiotherapy. There was a significant correlation between functionally intact telomeres and the cellular response to ionising radiation. Our findings suggest that fluorescence in situ hybridisation on micronuclei could be effectively used as routine clinical application to determine the individual sensitivity to ionising radiation with respect to telomere damage.
authors.affiliation: Department of Medical Genetics, Manipal Hospital, Bangalore, India.
authors.forename: Birendranath
authors.initials: B
authors.lastname: Banerjee
authors.forename: Sanjiv
authors.initials: S
authors.lastname: Sharma
authors.forename: Sridevi
authors.initials: S
authors.lastname: Hegde
authors.forename: M Prakash
authors.initials: MP
authors.lastname: Hande
mesh_terms: D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000378:metabolism* / Q000532:radiotherapy / Q000648:ultrastructure*; D002277:Carcinoma / Q000378:metabolism* / Q000532:radiotherapy / Q000648:ultrastructure*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D020847:Estrogen Receptor Modulators / Q000378:metabolism; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods*; D048629:Micronuclei, Chromosome-Defective; D011110:Polymorphism, Genetic; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D016615:Telomere / Q000648:ultrastructure*; D053781:Transforming Growth Factor beta2 / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D020847:Estrogen Receptor Modulators; D018125:Receptors, Transforming Growth Factor beta; D053781:Transforming Growth Factor beta2; D003577:Cytochrome P-450 Enzyme System; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II