Abstract 2403: Imaging of UVB and UVC-induced DNA damage repair in cancer cells in Gelfoam histoculture and minimal cancer in mice

Abstract

Abstract We compared the DNA damage repair response of cancer cells after UVB or UVC irradiation. The DNA-damage repair response to UV irradiation was imaged in tumors growing in 3D Gelfoam® histoculture and in superficial tumors grown in mice. UV-induced DNA damage repair was imaged with GFP fused to the DNA damage response (DDR)-related chromatin-binding protein 53BP1 in MiaPaCa-2 human pancreatic cancer cells. 53BP1 forms foci during DNA damage repair. A clonogenic assay initially showed that UVC and UVB inhibited MiaPaCa-2 cell proliferation in a dose-dependent manner, with UVC having more efficacy. Gelfoam® histocultures and confocal imaging enabled 53BP1-GFP nuclear foci to be observed within 1 h after UV irradiation, indicating the onset of DNA damage repair response. Induction of UVB-induced 53BP1-GFP focus formation was observed up to a depth of 120 µm in MiaPaCa-2 cells on Gelfoam®, while UVC induced foci only to a depth of 40 µm. The MiaPaCa-2 cells irradiated by both UVB and UVC light in a skin-flap mouse model had a significant decrease in tumor growth compared to untreated controls. Moreover, UVB-treatment had greater inhibition of tumor growth compared to UVC. Our results demonstrate that both UVB and UVC are useful tools for the treatment of residual cancer, and UVB was more effective than UVC in vivo, possibly due to greater tissue penetration of UVB because of its longer wavelength. Citation Format: Fuminari Uehara, Shinji Miwa, Yasunori Tome, Hiroki Maehara, Fuminori Kanaya, Yukihiko Hiroshima, Shuya Yano, Mako Yamamoto, Yasunori Matsumoto, Elena V. Efimova, Robert M. Hoffman. Imaging of UVB and UVC-induced DNA damage repair in cancer cells in Gelfoam histoculture and minimal cancer in mice. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2403. doi:10.1158/1538-7445.AM2014-2403