title: Imaging UVC-induced DNA damage response in models of minimal cancer.
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.
authors.affiliation: AntiCancer, Inc., San Diego, California; Department of Surgery, University of California, San Diego, California; Department of Orthopaedic Surgery, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Miwa
authors.forename: Shuya
authors.initials: S
authors.lastname: Yano
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Hiroshima
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Tome
authors.forename: Fuminari
authors.initials: F
authors.lastname: Uehara
authors.forename: Sumiyuki
authors.initials: S
authors.lastname: Mii
authors.forename: Elena V
authors.initials: EV
authors.lastname: Efimova
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kimura
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Hayashi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tsuchiya
authors.forename: Robert M
authors.initials: RM
authors.lastname: Hoffman
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000528:radiation effects; D004249:DNA Damage / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009369:Neoplasms / Q000235:genetics*; D014466:Ultraviolet Rays
keywords: 53BP1; DNA DAMAGE; GFP; MIAPACA-2; NUDE MICE; PANCREATIC CANCER; REPAIR RESPONSE; SKIN FLAP; THREE-DIMENSIONAL CULTURE IMAGING; UVC