title: DNA Damage in Peripheral Blood Lymphocytes of Thyroid Cancer Patients After Radioiodine Therapy.
abstract: The aim of the study was to investigate DNA double-strand break (DSB) formation and its correlation to the absorbed dose to the blood in patients with surgically treated differentiated thyroid cancer undergoing their first radioiodine therapy for remnant ablation.
  
  
  METHODS
  Twenty patients were included in this study. At least 7 peripheral blood samples were obtained before and between 0.5 and 120 h after administration of radioiodine. From the time-activity curves of the blood and the whole body, residence times for the blood self-irradiation and the irradiation from the whole body were determined. Peripheral blood lymphocytes were isolated, ethanol-fixed, and subjected to immunofluorescence staining for colocalizing γ-H2AX/53BP1 DSB-marking foci. The average number of DSB foci per cell per patient sample was analyzed as a function of the absorbed dose to the blood and compared with an in vitro calibration curve for (131)I and (177)Lu established previously in our institution.
  
  
  RESULTS
  The average number of radiation-induced foci (RIF) per cell increased over the first 3 h after radionuclide administration and decreased thereafter. A linear fit from 0 to 2 h as a function of the absorbed dose to the blood agreed with our in vitro calibration curve. At later time points, RIF numbers diminished, along with dropping dose rates, indicating progression of DNA repair. Individual patient data were characterized by a linear dose-dependent increase and a biexponential response function describing a fast and a slow repair component.
  
  
  CONCLUSIONS
  With the experimental results and model calculations presented in this work, a dose-response relationship is demonstrated, and an analytic function describing the time course of the in vivo damage response after internal irradiation of patients with (131)I is established.
authors.affiliation: Department of Nuclear Medicine, University of Würzburg, Germany; and.
authors.forename: Uta
authors.initials: U
authors.lastname: Eberlein
authors.affiliation: Bundeswehr Institute of Radiobiology affiliated to the University of Ulm, Munich, Germany.
authors.forename: Harry
authors.initials: H
authors.lastname: Scherthan
authors.affiliation: Department of Nuclear Medicine, University of Würzburg, Germany; and.
authors.forename: Christina
authors.initials: C
authors.lastname: Bluemel
authors.affiliation: Bundeswehr Institute of Radiobiology affiliated to the University of Ulm, Munich, Germany.
authors.forename: Michel
authors.initials: M
authors.lastname: Peper
authors.affiliation: Department of Nuclear Medicine, University of Würzburg, Germany; and.
authors.forename: Constantin
authors.initials: C
authors.lastname: Lapa
authors.affiliation: Department of Nuclear Medicine, University of Würzburg, Germany; and.
authors.forename: Andreas Konrad
authors.initials: AK
authors.lastname: Buck
authors.affiliation: Bundeswehr Institute of Radiobiology affiliated to the University of Ulm, Munich, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Port
authors.affiliation: Department of Nuclear Medicine, University of Würzburg, Germany; and Lassmann_m@ukw.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Lassmann
mesh_terms: D000328:Adult; D000368:Aged; D004249:DNA Damage / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006657:Histones / Q000097:blood; D006801:Humans; D007457:Iodine Radioisotopes / Q000009:adverse effects* / Q000627:therapeutic use*; D008187:Lutetium; D018655:Lymphocyte Count; D008214:Lymphocytes / Q000528:radiation effects*; D008297:Male; D008875:Middle Aged; D011829:Radiation Dosage; D011868:Radioisotopes; D019275:Radiopharmaceuticals / Q000009:adverse effects* / Q000627:therapeutic use*; D013964:Thyroid Neoplasms / Q000532:radiotherapy*; D014916:Whole-Body Irradiation
chemical_list: C468783:H2AX protein, human; D006657:Histones; D007457:Iodine Radioisotopes; D011868:Radioisotopes; D019275:Radiopharmaceuticals; D008187:Lutetium
keywords: 131I; 53BP1; DNA damage; DSB focus assay; DTC; absorbed dose to blood; biological dosimetry; differentiated thyroid cancer; dose response; radioiodine therapy; γ-H2AX