Abstract
The oxidative stress caused by low LET radiation is considered as a risk factor to induce alteration of genetic information. In DNA, among four bases, guanine is most susceptible to oxidation, and its simple oxidized form is 8-oxoguanine (8-oxoG). 8-OxoG is a potent pre-mutagenic lesion because it can pair with adenine as well as with cytosine during DNA replication.
To investigate the oxidative DNA damage caused by reactive oxygen species as an indirect effect of low LET radiation on various cell type, we examined the intestines of wild-type mice received a whole-body irradiation. Using immuno-histochemical method, we detected 8-oxoG in both nuclear DNA and mitochondrial DNA. At 1 hour post irradiation (X-ray, 4 and 10 Gy, 1 Gy/min), we observed only slightly increased 8-oxoG in nuclear DNA of intestinal epithelial cells in both villi (non-proliferative cells) and crypt regions (proliferative cell rich). In contrast to the nuclear signal, a significant increase of mitochondrial 8-oxoG in villous epithelial cells (but not in cryptic cells) was observed.
To clarify the oxygen effect, we analyzed cellular oxygen consumption of intestinal epithelial cells by Hypoxiprobe-1. In the intestine of non-irradiated mice, the villous cells were more hypoxic compared to the cryptic cells, however after radiation, oxygen consumption in villous cells increased. These results suggest that X-ray radiation increases the level of 8-oxoG predominantly in mitochondrial DNA and may lead prolonged oxidative stress caused by mitochondrial disfunction.
