title: Influence of double-strand break repair on radiation therapy-induced acute skin reactions in breast cancer patients.
abstract: OBJECTIVE
  Curative radiation therapy (RT)-induced toxicity poses strong limitations for efficient RT and worsens the quality of life. The parameter that explains when and to what extent normal tissue toxicity in RT evolves would be of clinical relevance because of its predictive value and may provide an opportunity for personalized treatment approach.
  
  
  METHODS
  DNA double-strand breaks and repair were analyzed by microscopic γ-H2AX foci analysis in peripheral lymphocytes from 38 healthy donors and 80 breast cancer patients before RT, a 2 Gy challenge dose of x-ray exposed in vitro.
  
  
  RESULTS
  The actual damage (AD) at 0.25, 3, and 6 hours and percentage residual damage (PRD) at 3 and 6 hours were used as parameters to measure cellular radiosensitivity and correlated with RT-induced acute skin reactions in patients stratified as non-overresponders (NOR) (Radiation Therapy Oncology Group [RTOG] grade <2) and overresponders (OR) (RTOG grade ≥2). The results indicated that the basal and induced (at 0.25 and 3 hours) γ-H2AX foci numbers were nonsignificant (P>.05) between healthy control donors and the NOR and OR groups, whereas it was significant between ORs and healthy donors at 6 hours (P<.001). There was a significantly higher PRD in OR versus NOR (P<.05), OR versus healthy donors (P<.001) and NOR versus healthy donors (P<.01), supported further by the trend analysis (r=.2392; P=.0326 at 6 hours).
  
  
  CONCLUSIONS
  Our findings strongly suggest that the measurement of PRD by performing γ-H2AX foci analysis has the potential to be developed into a clinically useful predictive assay.
authors.affiliation: Division of Radiobiology and Toxicology, School of Life Sciences, Manipal University, Manipal, Karnataka, India.
authors.forename: Kamalesh Dattaram
authors.initials: KD
authors.lastname: Mumbrekar
authors.affiliation: Department of Radiotherapy and Oncology, Shirdi Sai Baba Cancer Hospital and Research Centre, Kasturba Hospital, Manipal, Karnataka, India.
authors.forename: Donald Jerard
authors.initials: DJ
authors.lastname: Fernandes
authors.affiliation: Division of Radiobiology and Toxicology, School of Life Sciences, Manipal University, Manipal, Karnataka, India.
authors.forename: Hassan Venkatesh
authors.initials: HV
authors.lastname: Goutham
authors.affiliation: Department of Radiotherapy and Oncology, Shirdi Sai Baba Cancer Hospital and Research Centre, Kasturba Hospital, Manipal, Karnataka, India.
authors.forename: Krishna
authors.initials: K
authors.lastname: Sharan
authors.affiliation: Manipal Hospital, Bangalore, Karnataka, India.
authors.forename: Bejadi Manjunath
authors.initials: BM
authors.lastname: Vadhiraja
authors.affiliation: Division of Biotechnology, School of Life Sciences, Manipal University, Manipal, Karnataka, India.
authors.forename: Kapaettu
authors.initials: K
authors.lastname: Satyamoorthy
authors.affiliation: Division of Radiobiology and Toxicology, School of Life Sciences, Manipal University, Manipal, Karnataka, India. Electronic address: satishraomlsc@gmail.com.
authors.forename: Satish Rao
authors.initials: SR
authors.lastname: Bola Sadashiva
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000032:analysis; D001943:Breast Neoplasms / Q000235:genetics / Q000532:radiotherapy*; D053903:DNA Breaks, Double-Stranded; D004249:DNA Damage / Q000235:genetics; D004260:DNA Repair / Q000235:genetics*; D005260:Female; D006657:Histones / Q000032:analysis* / Q000235:genetics; D006801:Humans; D008214:Lymphocytes / Q000528:radiation effects; D008875:Middle Aged; D016017:Odds Ratio; D011446:Prospective Studies; D011832:Radiation Injuries / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D012867:Skin / Q000378:metabolism / Q000528:radiation effects*
chemical_list: D015415:Biomarkers; C468783:H2AX protein, human; D006657:Histones