title: A novel parameter, cell-cycle progression index, for radiation dose absorbed estimation in the premature chromosome condensation assay.
abstract: The calyculin A-induced premature chromosome condensation (PCC) assay is a simple and useful method for assessing the cell-cycle distribution in cells, since calyculin A induces chromosome condensation in various phases of the cell cycle. In this study, a novel parameter, the cell-cycle progression index (CPI), in the PCC assay was validated as a novel biomarker for biodosimetry. Peripheral blood was drawn from healthy donors after informed consent was obtained. CPI was investigated using a human peripheral blood lymphocyte (PBL) ex vivo irradiation ((60)Co-gamma rays: ∼0.6 Gy min(-1), or X ray: 1.0 Gy min(-1); 0-10 Gy) model. The calyculin A-induced PCC assay was performed for chromosome preparation. PCC cells were divided into the following five categories according to cell-cycle stage: non-PCC, G1-PCC, S-PCC, G2/M-PCC and M/A-PCC cells. CPI was calculated as the ratio of G2/M-PCC cells to G1-PCC cells. The PCC-stage distribution varied markedly with irradiation doses. The G1-PCC cell fraction was significantly reduced, and the G2/M-PCC cell fraction increased, in 10-Gy-irradiated PBL after 48 h of culture. CPI levels were fitted to an exponential dose-response curve with gamma-ray irradiation [y = 0.6729 + 0.3934 exp(0.5685D), r = 1.0000, p < 0.0001] and X-ray irradiation [y = -0.3743 + 0.9744 exp(0.3321D), r = 0.9999, p < 0.0001]. There were no significant individual (p = 0.853) or gender effects (p = 0.951) on the CPI in the human peripheral blood ex vivo irradiation model. Furthermore, CPI measurements are rapid (< 15 min per case). These results suggest that the CPI is a useful screening tool for the assessment of radiation doses received ranging from 0 to 10 Gy in radiation exposure early after a radiation event, especially after a mass-casualty radiological incident.
authors.affiliation: Department of Biomedical Sciences, Hirosaki University Graduate School of Health Sciences, 66-1 Hon-cho, Hirosaki 036-8564, Japan tomisato@cc.hirosaki-u.ac.jp.
authors.forename: Tomisato
authors.initials: T
authors.lastname: Miura
authors.affiliation: Hirosaki University, Institute of Radiation Emergency Medicine, 66-1 Hon-cho, Hirosaki 036-8564, Japan.
authors.forename: Akifumi
authors.initials: A
authors.lastname: Nakata
authors.affiliation: Department of Biomedical Sciences, Hirosaki University Graduate School of Health Sciences, 66-1 Hon-cho, Hirosaki 036-8564, Japan.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Kasai
authors.affiliation: Department of Biomedical Sciences, Hirosaki University Graduate School of Health Sciences, 66-1 Hon-cho, Hirosaki 036-8564, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Nakano
authors.affiliation: Department of Biomedical Sciences, Hirosaki University Graduate School of Health Sciences, 66-1 Hon-cho, Hirosaki 036-8564, Japan Department of Radiation Life Sciences, Fukushima Medical University, 1 Hikariga-oka, Fukushima 960-1295, Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Abe
authors.affiliation: Department of Development and Aging, Hirosaki University Graduate School of Health Sciences, 66-1 Hon-cho, Hirosaki 036-8564, Japan.
authors.forename: Eiki
authors.initials: E
authors.lastname: Tsushima
authors.affiliation: Armed Forces Radiobiology Research Institute (AFRRI), Uniformed Services University of the Health Sciences (USUHS), Bethesda, MD 20889, USA.
authors.forename: Natalia I
authors.initials: NI
authors.lastname: Ossetrova
authors.affiliation: Hirosaki University, Institute of Radiation Emergency Medicine, 66-1 Hon-cho, Hirosaki 036-8564, Japan.
authors.forename: Mitsuaki A
authors.initials: MA
authors.lastname: Yoshida
authors.affiliation: Armed Forces Radiobiology Research Institute (AFRRI), Uniformed Services University of the Health Sciences (USUHS), Bethesda, MD 20889, USA.
authors.forename: William F
authors.initials: WF
authors.lastname: Blakely
mesh_terms: D001681:Biological Assay / Q000379:methods*; D002273:Carcinogens / Q000494:pharmacology; D002453:Cell Cycle / Q000235:genetics / Q000528:radiation effects*; D002478:Cells, Cultured; D002877:Chromosomes, Human / Q000187:drug effects / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects / Q000528:radiation effects*; D008297:Male; D008387:Marine Toxins; D010080:Oxazoles / Q000494:pharmacology; D011832:Radiation Injuries / Q000175:diagnosis* / Q000235:genetics; D014965:X-Rays
chemical_list: D002273:Carcinogens; D008387:Marine Toxins; D010080:Oxazoles; C059041:calyculin A