title: Biodosimetry Based on γ-H2AX Quantification and Cytogenetics after Partial- and Total-Body Irradiation during Fractionated Radiotherapy.
abstract: The aim of this current study was to quantitatively describe radiation-induced DNA damage and its distribution in leukocytes of cancer patients after fractionated partial- or total-body radiotherapy. Specifically, the impact of exposed anatomic region and administered dose was investigated in breast and prostate cancer patients receiving partial-body radiotherapy. DNA double-strand breaks (DSBs) were quantified by γ-H2AX immunostaining. The frequency of unstable chromosomal aberrations in stimulated lymphocytes was also determined and compared with the frequency of DNA DSBs in the same samples. The frequency of radiation-induced DNA damage was converted into dose, using ex vivo generated calibration curves, and was then compared with the administered physical dose. This study showed that 0.5 h after partial-body radiotherapy the quantity of radiation-induced γ-H2AX foci increased linearly with the administered equivalent whole-body dose for both tumor entities. Foci frequencies dropped 1 day thereafter but proportionality to the equivalent whole-body dose was maintained. Conversely, the frequency of radiation-induced cytogenetic damage increased from 0.5 h to 1 day after the first partial-body exposure with a linear dependence on the administered equivalent whole-body dose, for prostate cancer patients only. Only γ-H2AX foci assessment immediately after partial-body radiotherapy was a reliable measure of the expected equivalent whole-body dose. Local tumor doses could be approximated with both assays after one day. After total-body radiotherapy satisfactory dose estimates were achieved with both assays up to 8 h after exposure. In conclusion, the quantification of radiation-induced γ-H2AX foci, but not cytogenetic damage in peripheral leukocytes was a sensitive and rapid biodosimeter after acute heterogeneous irradiation of partial body volumes that was able to primarily assess the absorbed equivalent whole-body dose.
authors.affiliation: a  Department of Radiation Oncology and Radiotherapy, University Medical Center Johannes Gutenberg University Mainz, 55131 Mainz, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Zahnreich
authors.forename: Anne
authors.initials: A
authors.lastname: Ebersberger
authors.forename: Bernd
authors.initials: B
authors.lastname: Kaina
authors.forename: Heinz
authors.initials: H
authors.lastname: Schmidberger
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002138:Calibration; D002869:Chromosome Aberrations / Q000528:radiation effects; D020732:Cytogenetic Analysis; D004249:DNA Damage; D019583:Dose Fractionation, Radiation; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006657:Histones / Q000378:metabolism*; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism / Q000528:radiation effects; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000532:radiotherapy*; D011832:Radiation Injuries / Q000097:blood / Q000235:genetics*; D011836:Radiation Tolerance; D011874:Radiometry; D011880:Radiotherapy Planning, Computer-Assisted; D014916:Whole-Body Irradiation / Q000009:adverse effects*; D055815:Young Adult
chemical_list: C468783:H2AX protein, human; D006657:Histones