title: Reactive oxygen species mediated tissue damage in high energy proton irradiated mouse brain.
abstract: Although radiation related research has been conducted extensively, the molecular toxicology and cellular mechanisms affected by proton radiation remain poorly understood. We recently reported that the high energy protons induce cell death through activation of apoptotic signaling genes; caspase 3 and 8 (Baluchamy et al. J Biol Chem 285:24769-24774, 2010). In this study, we investigated the effect of different doses of protons in in vivo mouse system, particularly, brain tissues. A significant dose-dependent induction of reactive oxygen species and lipid peroxidation and reduction of antioxidants; glutathione and superoxide dismutase were observed in proton irradiated mouse brain as compared to control brain. Furthermore, histopathology studies on proton irradiated mouse brain showed significant tissue damage as compared to control brain. Together, our in vitro and in vivo results suggest that proton irradiation alters oxidant and antioxidant levels in the cells to cause proton mediated DNA/tissue damage followed by apoptotic cell death.
authors.affiliation: Department of Biotechnology, Pondicherry University, Puducherry, India.
authors.forename: Sudhakar
authors.initials: S
authors.lastname: Baluchamy
authors.forename: Prabakaran
authors.initials: P
authors.lastname: Ravichandran
authors.forename: Vani
authors.initials: V
authors.lastname: Ramesh
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: He
authors.forename: Ye
authors.initials: Y
authors.lastname: Zhang
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Hall
authors.forename: Olufisayo
authors.initials: O
authors.lastname: Jejelowo
authors.forename: Daila S
authors.initials: DS
authors.lastname: Gridley
authors.forename: Honglu
authors.initials: H
authors.lastname: Wu
authors.forename: Govindarajan T
authors.initials: GT
authors.lastname: Ramesh
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001921:Brain / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects*; D005978:Glutathione / Q000378:metabolism; D015227:Lipid Peroxidation / Q000528:radiation effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011522:Protons / Q000009:adverse effects; D011832:Radiation Injuries / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism; D000072105:Superoxide Dismutase-1; D000099156:Superoxide Dismutase 2
chemical_list: D000975:Antioxidants; D005978:Glutathione; D011522:Protons; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D000099156:Superoxide Dismutase 2; C000606291:Sod1 protein, mouse