title: γ-H2AX Kinetic Profile in Mouse Lymphocytes Exposed to the Internal Emitters Cesium-137 and Strontium-90.
abstract: In the event of a dirty bomb scenario or an industrial nuclear accident, a significant dose of volatile radionuclides such as 137Cs and 90Sr may be dispersed into the atmosphere as a component of fallout and inhaled or ingested by hundreds and thousands of people. To study the effects of prolonged exposure to ingested radionuclides, we have performed long-term (30 day) internal-emitter mouse irradiations using soluble-injected 137CsCl and 90SrCl2 radioisotopes. The effect of ionizing radiation on the induction and repair of DNA double strand breaks (DSBs) in peripheral mouse lymphocytes in vivo was determined using the γ-H2AX biodosimetry marker. Using a serial sacrifice experimental design, whole-body radiation absorbed doses for 137Cs (0 to 10 Gy) and 90Sr (0 to 49 Gy) were delivered over 30 days following exposure to each radionuclide. The committed absorbed doses of the two internal emitters as a function of time post exposure were calculated based on their retention parameters and their derived dose coefficients for each specific sacrifice time. In order to measure the kinetic profile for γ-H2AX, peripheral blood samples were drawn at 5 specific timed dose points over the 30-day study period and the total γ-H2AX nuclear fluorescence per lymphocyte was determined using image analysis software. A key finding was that a significant γ-H2AX signal was observed in vivo several weeks after a single radionuclide exposure. A mechanistically-motivated model was used to analyze the temporal kinetics of γ-H2AX fluorescence. Exposure to either radionuclide showed two peaks of γ-H2AX: one within the first week, which may represent the death of mature, differentiated lymphocytes, and the second at approximately three weeks, which may represent the production of new lymphocytes from damaged progenitor cells. The complexity of the observed responses to internal irradiation is likely caused by the interplay between continual production and repair of DNA damage, cell cycle effects and apoptosis.
authors.affiliation: Center for Radiological Research, Columbia University Medical Center, New York, New York, United States of America.
authors.forename: Helen C
authors.initials: HC
authors.lastname: Turner
authors.affiliation: Center for Radiological Research, Columbia University Medical Center, New York, New York, United States of America.
authors.forename: Igor
authors.initials: I
authors.lastname: Shuryak
authors.affiliation: Lovelace Respiratory Research Institute, Albuquerque, New Mexico, United States of America.
authors.forename: Waylon
authors.initials: W
authors.lastname: Weber
authors.affiliation: Lovelace Respiratory Research Institute, Albuquerque, New Mexico, United States of America.
authors.forename: Melanie
authors.initials: M
authors.lastname: Doyle-Eisele
authors.affiliation: Lovelace Respiratory Research Institute, Albuquerque, New Mexico, United States of America.
authors.forename: Dunstana
authors.initials: D
authors.lastname: Melo
authors.affiliation: Lovelace Respiratory Research Institute, Albuquerque, New Mexico, United States of America.
authors.forename: Raymond
authors.initials: R
authors.lastname: Guilmette
authors.affiliation: Center for Radiological Research, Columbia University Medical Center, New York, New York, United States of America.
authors.forename: Sally A
authors.initials: SA
authors.lastname: Amundson
authors.affiliation: Center for Radiological Research, Columbia University Medical Center, New York, New York, United States of America.
authors.forename: David J
authors.initials: DJ
authors.lastname: Brenner
mesh_terms: D000818:Animals; D017209:Apoptosis; D002453:Cell Cycle / Q000528:radiation effects; D002588:Cesium Radioisotopes / Q000633:toxicity*; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D006657:Histones / Q000097:blood*; D007700:Kinetics; D008214:Lymphocytes / Q000166:cytology / Q000528:radiation effects*; D051379:Mice; D013326:Strontium Radioisotopes / Q000633:toxicity*; D014916:Whole-Body Irradiation
chemical_list: D002588:Cesium Radioisotopes; C468783:H2AX protein, human; D006657:Histones; D013326:Strontium Radioisotopes