Transgenerational Radiation Epigenetics
Final rept. 1 Sep 2010-31 Aug 2014
FRED HUTCHINSON CANCER RESEARCH CENTER SEATTLE WA
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Ionizing radiation is a human carcinogen to which the military has increased risk of exposure. Radiation causes DNA damage and is a potent mutagen. Radiation also has epigenetic affects and may affect transgenerational cancer risk. Here we set out to determine if exposure to low dose radiation in utero leads to a change in DNA methylation in adult tissues and in ensuing unexposed generations, and if these changes correlate with increased cancer susceptibility. We report that a single dose of 0.5 Gy radiation at day 15 of embryogenesis increased lung cancer incidence in Balbc mice and also resulted in reduced body weight. Examination of DNA methylation at 38 lung cancer relevant genes in normal lung tissue identified four that showed hypermethylation. We did not detect differential methylation between irradiated and control mice for these 38 genes. Examination of expression of 320 cancer related genes identified 12 that showed either an increase or decrease in expression in irradiated young adult mice relative to control mice. Seven genes also showed altered expression in normal lung from F3 mice. Thus, traces of the effects of a single dose of radiation during development persist into adulthood and may extend to subsequent generations. Five of the 12 genes that show altered expression in irradiated normal lung also showed altered expression in lung tumors and there was heterogeneity between individual lung tumors. We have generated an extensive tissue repository for future studies on the epigenetic and transgenerational effects of low dose radiation.
- Medicine and Medical Research