Effects of low dose ionizing radiation on transcriptional expression of DNA repair and reactive oxygen species scavenging genes: Studies at Chornobyl

Abstract

Ionizing radiation (IR) can initiate a large spectrum of damage which leads to the induction of DNA protective and repair pathways. Historically, IR studies have assessed the effects of high dose, acute exposures; however a recent shift in radiation biology has focused its efforts to cellular responses of low dose IR exposure. We used the radioactive environment surrounding the Chornobyl Nuclear Power Plant to assess the potential for the development of radioresistance in exposed animals and the possible molecular mechanisms that maybe responsible. To better understand the phenomenon of radioresistance, we exposed male BALB/c mice externally to a priming (pr) dose of 10cGy at two dose rates (6.94x10-4cGy min-1 and 0.5cGy min-1) followed by a subsequent 1.5Gy challenge (ch) dose (6.25x10-3Gy min-1). We measured absolute mRNA levels using quantitative real-time polymerase chain reaction (QRT-PCR) of enzymes and proteins believed to maintain genome integrity under increased levels of oxidative stress. Twenty four hours post exposure there was no induction of Apex1 and Polb (Base Excision Repair [BER]), Ercc1 and Ercc2 (Nucleotide Excision Repair [NER]) and Gpx1 (Reactive Oxygen Species [ROS] scavenging). We were able to detect a significant amount of differential expression in two of our exposure groups for the Sod1 (ROS scavenging) gene. When compared to micronucleus (MN) data as a measurement of radioadaption of these same mice, the high expression levels of Sod1 suggest a temporal-dependent component. Therefore, we conclude that Sod1 expression levels suggest a role in radioadaption at ultra-low dose rates.