3902

High doses of ionizing radiation cause DNA damage and cancer. However, little is known about the potential deleterious effects of elevated chronic low dose radiation experienced by people living in certain locations or working in certain occupations. In the absence of data, low dose radiation effects have been estimated by linearly extrapolating the known DNA damage data of high dose radiation. However, this linear correlation might not accurately reflect low dose radiation effects. Here we set out to experimentally establish a comprehensive view of chronic low dose radiation effects on DNA damage in vivo.

To initiate these studies, we created a novel exposure apparatus that allows for long-term continuous exposure of mice at very low radiation doses using 125Iodine as the radioactive source. Prior to and during experiments we performed extensive dosimetry using Luxel OSL dosimeters to assess dose rate and uniformity of the exposure field. Having established conditions that permit long-term exposure to 0.3 cGy/day (equal to approximately 300X background levels of radiation), we exposed 4 week old C57Bl6 mice (n=16) for 5 weeks to achieve a total dose of 10.5 cGy. A control cohort of sex-matched littermates (n=16) was housed in the same facility. After 5 weeks, animals were humanely sacrificed and tissues were isolated for further analysis. Focusing on the hematopoietic system as one of the most radiation sensitive tissues, we did not detect a statistical difference in blood counts between control and irradiated animals. Moreover, red blood cell micronuclei frequency did not differ between the control (0.47%) and irradiated (0.54%) cohorts.

Using a combination of HPLC and mass spectrometry, we are able to measure spontaneous levels of several DNA base lesions known to be created by ionizing radiation. We assessed their levels in control and irradiated spleens but did not detect any differences in the amounts of 8-oxoGuanine (8.6 vs 6.7 per 106 nt), deoxyuridine (11.8 vs. 9.8 per 106 nt), or ethenoadenine (4.5 vs. 4.4 per 107 nt), which suggests that low dose radiation at 0.3 cGy/day is not able to affect DNA base lesion homeostasis. Finally, we also investigated the influence of low dose chronic irradiation on DNA double strand break repair using a transgenic mouse model in which homologous recombination events at a transgenic reporter give rise to fluorescent cells. No significant difference was observed in the frequency of recombinant cells in the skin or in the pancreas (pancreas, 23 vs. 17 /106 cells; skin, 1.7 vs. 1.6 /106 cells; n=24 per cohort).

These experiments demonstrate that ionizing radiation at a dose rate that is 300 fold higher than background levels does not induce a significant change in either the levels of DNA base lesions or the frequency of homologous recombination. Therefore, these results are consistent with the possibility that a threshold exists, below which no deleterious radiation effects can be observed.

98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA