title: γH2AX formation kinetics in PBMCs of rabbits exposed to acute and fractionated radiation and attenuation of focus frequency through preadministration of a combination of podophyllotoxin and rutin hydrate.
abstract: DNA damage can be assessed by the quantitation of γH2AX foci that form at DSB sites. This study examines the generation and persistence of γH2AX foci, variability in foci size after acute and fractionated radiation exposure, and the effect of pretreatment with a safe radioprotective formulation termed G-003M on foci generation and persistence. G-003M contains a combination of podophyllotoxin and rutin hydrate, and was administered intramuscularly to rabbits 1 hr prior to Co(60) gamma irradiation. Rabbits were assigned to one of the following treatment groups: untreated, G-003M alone, irradiated (single dose 8 Gy, fractionated 2 Gy/day for 4 days or single dose 2 Gy) or G-003M preadministration followed by radiation exposure. Foci continuously persisted for a week in peripheral blood mononuclear cells of rabbits exposed to a single 8 Gy dose. However, the number of foci gradually decreased after reaching a maximum at 1 h. In rabbits exposed to fractionated radiation, foci detected 1 hr after the final exposure were significantly larger (P < 0.001) than in rabbits exposed to a single 8 Gy dose, but disappeared completely after 24 h. In both groups, foci reappeared on days 11-15 in terminally ill animals. G-003M pretreatment significantly (P < 0.05) attenuated the formation of γH2AX foci in all irradiated rabbits. This study reveals that γH2AX focus assessment could be used to confirm radiation exposure, that focus size reflects the type of radiation exposure (acute or fractionated), that the re-appearance of foci is a strong indicator of imminent death in animals, and that G-003M provides protection against radiation. Environ. Mol. Mutagen. 57:455-468, 2016. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Division of Radioprotective Drug Development Research, Institute of Nuclear Medicine and Allied Sciences (INMAS), DRDO, SK Mazumdar Marg, Delhi, 110054, India.|School of Biotechnology, KIIT University, Bhubaneswar, Odisha 751024, India.
authors.forename: M H
authors.initials: MH
authors.lastname: Yashavarddhan
authors.affiliation: Division of Radioprotective Drug Development Research, Institute of Nuclear Medicine and Allied Sciences (INMAS), DRDO, SK Mazumdar Marg, Delhi, 110054, India.
authors.forename: Sandeep K
authors.initials: SK
authors.lastname: Shukla
authors.affiliation: Division of Radioprotective Drug Development Research, Institute of Nuclear Medicine and Allied Sciences (INMAS), DRDO, SK Mazumdar Marg, Delhi, 110054, India.
authors.forename: Nitya N
authors.initials: NN
authors.lastname: Srivastava
authors.affiliation: School of Biotechnology, KIIT University, Bhubaneswar, Odisha 751024, India.
authors.forename: Mrutyunjay
authors.initials: M
authors.lastname: Suar
authors.affiliation: Division of Radioprotective Drug Development Research, Institute of Nuclear Medicine and Allied Sciences (INMAS), DRDO, SK Mazumdar Marg, Delhi, 110054, India.
authors.forename: Sangeeta
authors.initials: S
authors.lastname: Dutta
authors.affiliation: Division of Radioprotective Drug Development Research, Institute of Nuclear Medicine and Allied Sciences (INMAS), DRDO, SK Mazumdar Marg, Delhi, 110054, India.
authors.forename: Bhargab
authors.initials: B
authors.lastname: Kalita
authors.affiliation: Division of Radioprotective Drug Development Research, Institute of Nuclear Medicine and Allied Sciences (INMAS), DRDO, SK Mazumdar Marg, Delhi, 110054, India.
authors.forename: Rajiv
authors.initials: R
authors.lastname: Ranjan
authors.affiliation: Division of Radioprotective Drug Development Research, Institute of Nuclear Medicine and Allied Sciences (INMAS), DRDO, SK Mazumdar Marg, Delhi, 110054, India.
authors.forename: Abhinav
authors.initials: A
authors.lastname: Singh
authors.affiliation: Division of Radioprotective Drug Development Research, Institute of Nuclear Medicine and Allied Sciences (INMAS), DRDO, SK Mazumdar Marg, Delhi, 110054, India.
authors.forename: Sania
authors.initials: S
authors.lastname: Bajaj
authors.affiliation: Division of Radioprotective Drug Development Research, Institute of Nuclear Medicine and Allied Sciences (INMAS), DRDO, SK Mazumdar Marg, Delhi, 110054, India.
authors.forename: Manju L
authors.initials: ML
authors.lastname: Gupta
mesh_terms: D000818:Animals; D053903:DNA Breaks, Double-Stranded / Q000187:drug effects / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D004357:Drug Synergism; D005434:Flow Cytometry; D005720:Gamma Rays / Q000009:adverse effects*; D056426:Genetic Loci; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D007700:Kinetics; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects*; D008297:Male; D011034:Podophyllotoxin / Q000008:administration & dosage / Q000494:pharmacology*; D011817:Rabbits; D011829:Radiation Dosage; D011837:Radiation-Protective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D012431:Rutin / Q000008:administration & dosage / Q000494:pharmacology*; D014916:Whole-Body Irradiation
chemical_list: D006657:Histones; D011837:Radiation-Protective Agents; D012431:Rutin; D011034:Podophyllotoxin
keywords: DNA double-strand breaks (DSBs); gamma radiation; hematology; immunofluorescence; podophyllum hexandrum