title: Distinct increased outliers among 136 rectal cancer patients assessed by γH2AX.
abstract: BACKGROUND
  In recent years attention has focused on γH2AX as a very sensitive double strand break indicator. It has been suggested that γH2AX might be able to predict individual radiosensitivity. Our aim was to study the induction and repair of DNA double strand breaks labelled by γH2AX in a large cohort.
  
  
  METHODS
  In a prospective study lymphocytes of 136 rectal cancer (RC) patients and 59 healthy individuals were ex vivo irradiated (IR) and initial DNA damage was compared to remaining DNA damage after 2 Gy and 24 hours repair time and preexisting DNA damage in unirradiated lymphocytes. Lymphocytes were immunostained with anti-γH2AX antibodies and microscopic images with an extended depth of field were acquired. γH2AX foci counting was performed using a semi-automatic image analysis software.
  
  
  RESULTS
  Distinct increased values of preexisting and remaining γH2AX foci in the group of RC patients were found compared to the healthy individuals. Additionally there are clear differences within the groups and there are outliers in about 12% of the RC patients after ex vivo IR.
  
  
  CONCLUSIONS
  The γH2AX assay has the capability to identify a group of outliers which are most probably patients with increased radiosensitivity having the highest risk of suffering radiotherapy-related late sequelae.
authors.affiliation: Department of Radiation Oncology, Friedrich-Alexander-University of Erlangen-Nürnberg, Universitätsstraße 27, D-91054, Erlangen, Germany. jana.kroeber@gmx.net.
authors.forename: Jana
authors.initials: J
authors.lastname: Kroeber
authors.affiliation: Department of Radiation Oncology, Friedrich-Alexander-University of Erlangen-Nürnberg, Universitätsstraße 27, D-91054, Erlangen, Germany. Barbara.Wenger@klinik.uni-regensburg.de.
authors.forename: Barbara
authors.initials: B
authors.lastname: Wenger
authors.affiliation: Department of Radiation Oncology, Friedrich-Alexander-University of Erlangen-Nürnberg, Universitätsstraße 27, D-91054, Erlangen, Germany. manuela.schwegler@uk-erlangen.de.
authors.forename: Manuela
authors.initials: M
authors.lastname: Schwegler
authors.affiliation: Department of Nephropathology, University Hospitals and Friedrich-Alexander-University Erlangen-Nürnberg Institute of Pathology, 91054, Erlangen, Germany. christoph.daniel@uk-erlangen.de.
authors.forename: Christoph
authors.initials: C
authors.lastname: Daniel
authors.affiliation: Department of Radiation Oncology, Friedrich-Alexander-University of Erlangen-Nürnberg, Universitätsstraße 27, D-91054, Erlangen, Germany. manfred.schmidt@uk-erlangen.de.
authors.forename: Manfred
authors.initials: M
authors.lastname: Schmidt
authors.affiliation: Department of Radiation Oncology, University of Würzburg, 97080, Würzburg, Germany. Djuzenova_T@ukw.de.
authors.forename: Cholpon S
authors.initials: CS
authors.lastname: Djuzenova
authors.affiliation: Department of Radiation Oncology, University of Würzburg, 97080, Würzburg, Germany. polat_b@ukw.de.
authors.forename: Bülent
authors.initials: B
authors.lastname: Polat
authors.affiliation: Department of Radiation Oncology, University of Würzburg, 97080, Würzburg, Germany. Flentje_M@klinik.uni-wuerzburg.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Flentje
authors.affiliation: Department of Radiation Oncology, Friedrich-Alexander-University of Erlangen-Nürnberg, Universitätsstraße 27, D-91054, Erlangen, Germany. rainer.fietkau@uk-erlangen.de.
authors.forename: Rainer
authors.initials: R
authors.lastname: Fietkau
authors.affiliation: Department of Radiation Oncology, Friedrich-Alexander-University of Erlangen-Nürnberg, Universitätsstraße 27, D-91054, Erlangen, Germany. Luitpold.Distel@uk-erlangen.de.
authors.forename: Luitpold V
authors.initials: LV
authors.lastname: Distel
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D004249:DNA Damage; D004260:DNA Repair; D005260:Female; D005455:Fluorescent Antibody Technique; D005500:Follow-Up Studies; D006657:Histones / Q000378:metabolism*; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism* / Q000473:pathology / Q000528:radiation effects; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011836:Radiation Tolerance / Q000235:genetics; D012004:Rectal Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy; D012007:Rectum / Q000378:metabolism* / Q000473:pathology
chemical_list: C468783:H2AX protein, human; D006657:Histones