title: Antioxidant dietary supplementation in mice exposed to proton radiation attenuates expression of programmed cell death-associated genes.
abstract: Dietary antioxidants have radioprotective effects after ionizing radiation exposure that limit hematopoietic cell depletion. We sought to determine the mechanism of proton-induced hematopoietic cell death in animals receiving a moderate dose of whole-body proton radiation. In addition, animals were maintained on diets supplemented with or without dietary antioxidants. In the presence of the dietary antioxidants, total bone marrow mRNA and protein expression of apoptosis-related genes were decreased compared to the expression profiles in the irradiated mice not receiving the antioxidant formulation. These data confirm high-energy proton-induced gene expression of classical apoptosis markers including BAX, caspase-3 and PARP-1. Antioxidant supplementation resulted in decreased expression of these genes in addition to increased protein expression of the anti-apoptosis markers Bcl2 and Bcl-xL. In conclusion, oral supplementation with antioxidants appears to be an effective approach for radioprotection against hematopoietic cell death.
authors: Department of Radiation Oncology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
authors: J K
authors: JK
authors: Sanzari
authors: C
authors: C
authors: Wambi
authors: J S
authors: JS
authors: Lewis-Wambi
authors: A R
authors: AR
authors: Kennedy
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics* / Q000528:radiation effects; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D002452:Cell Count; D019587:Dietary Supplements; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000528:radiation effects*; D008297:Male; D051379:Mice; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D011522:Protons / Q000009:adverse effects*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D053773:Transforming Growth Factor beta1 / Q000235:genetics; D015854:Up-Regulation / Q000187:drug effects / Q000528:radiation effects; D014916:Whole-Body Irradiation / Q000009:adverse effects; D051020:bcl-X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D000975:Antioxidants; D019253:Proto-Oncogene Proteins c-bcl-2; D011522:Protons; D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1; D051020:bcl-X Protein