Imaging UVC-induced DNA damage response in models of minimal cancer

Shinji Miwa, Shuya Yano, Yukihiko Hiroshima, Yasunori Tome, Fuminari Uehara, Sumiyuki Mii, Elena V. Efimova, Hiroaki Kimura, Katsuhiro Hayashi, Hiroyuki Tsuchiya, Robert M. Hoffman

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14 Citations (Scopus)

Abstract

We have previously demonstrated that the ultraviolet (UV) light is effective against a variety of cancer cells in vivo as well as in vitro. In the present report, we imaged the DNA damage repair response of minimal cancer after UVC irradiation. DNA-damage repair response to UV irradiation was imaged on tumors growing in 3D culture and in superficial tumors grown in vivo. 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. Three-dimensional Gelfoam® histocultures and confocal imaging enabled 53BP1-GFP nuclear foci to be observed within 1 h after UVC irradiation, indicating the onset of DNA damage repair response. A clonogenic assay showed that UVC inhibited MiaPaCa-2 cell proliferation in a dose-dependent manner, while UVA and UVB showed little effect on cell proliferation. Induction of UV-induced 53BP1-GFP focus formation was limited up to a depth of 40 μm in 3D-culture of MiaPaCa-2 cells. The MiaPaCa-2 cells irradiated by UVC light in a skin-flap mouse model had a significant decrease of tumor growth compared to untreated controls. Our results also demonstrate that 53BP1-GFP is an imageable marker of UV-induced DNA damage repair response of minimal cancer and that UVC is a useful tool for the treatment of residual cancer since UVC can kill superficial cancer cells without damage to deep tissue.

Original languageEnglish
Pages (from-to)2493-2499
Number of pages7
JournalJournal of Cellular Biochemistry
Volume114
Issue number11
DOIs
Publication statusPublished - Nov 1 2013

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Keywords

  • 53BP1
  • DNA Damage
  • GFP
  • MIAPACA-2
  • Nude Mice
  • Pancreatic Cancer
  • Repair Response
  • Skin Flap
  • Three-Dimensional Culture Imaging
  • UVC

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Miwa, S., Yano, S., Hiroshima, Y., Tome, Y., Uehara, F., Mii, S., Efimova, E. V., Kimura, H., Hayashi, K., Tsuchiya, H., & Hoffman, R. M. (2013). Imaging UVC-induced DNA damage response in models of minimal cancer. Journal of Cellular Biochemistry, 114(11), 2493-2499. https://doi.org/10.1002/jcb.24599