Abstract 3464: Epigenetic mechanism is involved in depleted uranium-induced transformation in human lung epithelial cells

Depleted uranium (DU) is commonly used in military applications and is also used in civilian industry and thus exposure of soldiers and others is frequent and widespread. There is limited research information on the potential health hazards of DU exposure. In our study, we used the human bronchial epithelial cell line (BEP2D) to study the potential carcinogenic effects of DU. DNA strand breaks were observed at 25 ug/cm 2 DU treatment. We found that DU induces cell transformation including cell contact inhibition and anchorage independent phenotype. Doses of 0.25, 2.5 and 25 ug/cm 2 uranium trioxide induces 23, 24 and 17 growth foci in 30 dishes, respectively. These foci were cloned and were found to exhibit anchorage independent growth and an aneuploid phenotype. We next investigated DU-induced epigenetic modifications. We found that DU decreases trimethylated H3K9 (H3K9me3), along with inhibition of the DNA damage repair protein ATM. Our study demonstrates that DU-induced both genotoxicity and aberrant histone methylation which may contribute to its carcinogenesis. This work was supported by ARO grants # W911NF-04-1-0240 and W911NF-08-0333 (J.P.W.). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3464.