title: Prevention of DNA double-strand breaks induced by radioiodide-(131)I in FRTL-5 thyroid cells.
abstract: Radioiodine-131 released from nuclear reactor accidents has dramatically increased the incidence of papillary thyroid cancer in exposed individuals. The deposition of ionizing radiation in cells results in double-strand DNA breaks (DSB) at fragile sites, and this early event can generate oncogenic rearrangements that eventually cause cancer. The aims of this study were to develop a method to show DNA DSBs induced by (131)I in thyroid cells; to test monovalent anions that are transported by the sodium/iodide symporter to determine whether they prevent (131)I-induced DSB; and to test other radioprotective agents for their effect on irradiated thyroid cells. Rat FRTL-5 thyroid cells were incubated with (131)I. DSBs were measured by nuclear immunofluorescence using antibodies to p53-binding protein 1 or γH2AX. Incubation with 1-10 μCi (131)I per milliliter for 90 min resulted in a dose-related increase of DSBs; the number of DSBs increased from a baseline of 4-15% before radiation to 65-90% after radiation. GH3 or CHO cells that do not transport iodide did not develop DSBs when incubated with (131)I. Incubation with 20-100 μm iodide or thiocyanate markedly attenuated DSBs. Perchlorate was about 6 times more potent than iodide or thiocyanate(.) The effects of the anions were much greater when each was added 30-120 min before the (131)I. Two natural organic compounds recently shown to provide radiation protection partially prevented DSBs caused by (131)I and had an additive effect with perchlorate. In conclusion, we developed a thyroid cell model to quantify the mitogenic effect of (131)I. (131)I causes DNA DSBs in FRTL-5 cells and had no effect on cells that do not transport iodide. Perchlorate, iodide, and thiocyanate protect against DSBs induced by (131)I.
authors.affiliation: Endocrinology and Diabetes Division, West Los Angeles Veterans Affairs Medical Center, Los Angeles, California 90073, USA. jhershmn@ucla.edu
authors.forename: Jerome M
authors.initials: JM
authors.lastname: Hershman
authors.forename: Armen
authors.initials: A
authors.lastname: Okunyan
authors.forename: Yelena
authors.initials: Y
authors.lastname: Rivina
authors.forename: Sophie
authors.initials: S
authors.lastname: Cannon
authors.forename: Victor
authors.initials: V
authors.lastname: Hogen
mesh_terms: D000818:Animals; D000838:Anions / Q000378:metabolism; D002460:Cell Line; D053903:DNA Breaks, Double-Stranded / Q000187:drug effects*; D007455:Iodine / Q000494:pharmacology*; D007457:Iodine Radioisotopes; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D051381:Rats; D027981:Symporters / Q000378:metabolism; D013961:Thyroid Gland / Q000166:cytology*; D000099209:Sodium-Iodide Symporters
chemical_list: D000838:Anions; D007455:Iodine; D007457:Iodine Radioisotopes; D011837:Radiation-Protective Agents; D027981:Symporters; D000099209:Sodium-Iodide Symporters