title: Dose-rate effect on proliferation suppression in human cell lines continuously exposed to γ rays.
abstract: Irradiation time and dose rate are important factors in the evaluation of radiation risk for human health. We previously proposed a novel dose-rate effect model, the modified exponential (MOE) model, which predicts that radiation risks decline exponentially as the dose rate decreases. Here we show that, during the early phase of exposure, up to 1000 h, the proliferation of cells continuously exposed to γ rays at a constant dose rate is gradually suppressed, even as the total dose increases. This trend holds for a number of cell lines including tumor cells, nontransformed fibroblasts and leukocytes. The accumulation of total dose by longer exposure times does not increase this suppressive effect even in cells with a defective DNA repair system, suggesting that risk is determined solely by dose rate in the later phase. The dose-rate effect in the early phase follows the MOE model in DNA repair-proficient cell lines, while cells with impaired DNA-PK or ATM show no dose-rate effect. In the later phase, however, a certain dose-rate effect is observed even in mutant cell lines, and suppression of cell proliferation no longer follows the MOE model. Our results suggest that a distinct mechanism that can operate in the absence of intact DNA-PK or ATM influences the dose-rate effect in the later phase of continuous radiation exposure.
authors.affiliation: Institute of Research and Innovation, 1201 Takada, Kashiwa 277-0861, Japan. jmagae@sannet.ne.jp
authors.forename: Junji
authors.initials: J
authors.lastname: Magae
authors.forename: Chiharu
authors.initials: C
authors.lastname: Furukawa
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Ogata
mesh_terms: D001692:Biological Transport / Q000528:radiation effects; D001773:Blood Cells / Q000528:radiation effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000528:radiation effects; D053903:DNA Breaks, Double-Stranded / Q000528:radiation effects; D004260:DNA Repair / Q000528:radiation effects; D004171:Diploidy; D004307:Dose-Response Relationship, Radiation; D005347:Fibroblasts / Q000378:metabolism / Q000528:radiation effects; D005720:Gamma Rays / Q000009:adverse effects*; D006801:Humans; D008954:Models, Biological; D013936:Thymidine / Q000378:metabolism; D013997:Time Factors
chemical_list: D013936:Thymidine