The effects of antioxidants on gene expression following gamma-radiation (GR) and proton radiation (PR) in mice in vivo

Abstract

Ionizing radiation (IR) generates free radicals that interact randomly with a range of intracellular biomolecules that can result in lethal cellular injury. Therefore, IR-inflicted damage is a highly complex interplay of vastly different pathophysiological processes, including inflammation, epithelial regeneration, tissue remodeling, and fibrosis. The development of safe and effective radioprotectors that protect normal tissues following IR exposure is highly desirable. It was previously shown that dietary supplementation with an antioxidant (AOX) diet containing SeM (0.06 μg/g diet), α-lipoic acid (85.7 μg/g diet), NAC (171.4 μg/g diet), sodium ascorbate (142.8 μg/g diet), and vitamin E succinate (71.4μg/g diet) was an effective countermeasure to lethality in mice following γ-radiation (GR) and proton radiation (PR). Here we are examining the effect of the AOX diet on global gene expression following RBE-weighted doses of GR (7.0 Gy) and PR (6.4 Gy) in an attempt to gain further insight into the molecular mechanism of action of AOX diet in the context of radiation exposure. The AOX diet altered the expression pattern of several pro- and anti-apoptotic genes. Our data suggest that the AOX diet may alter IL6 signaling following GR and completely block the expression of the prokineticin PROK2, the ligand to the G protein-coupled receptors PROKR1 and PROKR2, which are involved in a number of pathophysiological processes.

Keywords::

• in vivo
• gene expression
• apoptosis
• radiation
• IL6
• antioxidant
• PROK2
• gamma-radiation
• proton radiation