Abstract 807: Parental radiation elicits increased intestinal tumorigenesis in the F1 generation of APCMin/+ and APC1638N/+ mice

Abstract

Abstract The risk of colorectal cancer (CRC) has been reported to increase with radiation exposures as well as with a positive family history. Radiation exposure has also been implicated in inducing heritable changes in parental germline cells and thus increasing risk of cancer in the offspring. However, effects of parental radiation exposure on trans-generational colorectal carcinogenesis in offspring have not been explored yet. We employed two well-characterized mouse models (APCMin/+ and APC1638N/+) of human CRC to determine trans-generational effects of low dose radiation on colorectal carcinogenesis. Male APCMin/+ and APC1638N/+, and female C57BL/6J mice were exposed to whole body 25 cGy of x rays. Mating was initiated two days after radiation exposure, F1 offspring were genotyped, and male and female APCMin/+ and APC1638N/+ were grouped and housed separately. APCMin/+ mice were euthanized 150 days after birth, APC1638N/+ mice after 210 days, and tumor frequency and size in intestine and colon were noted. Significantly increased intestinal tumor frequency and increased numbers of larger tumors were observed in F1 mice of irradiated parents relative to F1 mice of sham-irradiated parents. Greater trans-generational tumorigenic effects of radiation were observed in male offspring relative to female offspring. In conclusion, here we present an early report for the first time that low dose radiation exposure has a trans-generational effect on intestinal tumorigenesis with potential implications for radiation exposure-related human health consequences. Citation Format: Shubhankar Suman, Santosh Kumar, Bo-Hyun Moon, Ziling Fan, Albert J. Fornace, Kamal Datta. Parental radiation elicits increased intestinal tumorigenesis in the F1 generation of APCMin/+ and APC1638N/+ mice. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 807. doi:10.1158/1538-7445.AM2015-807