title: Comparison of UVB and UVC effects on the DNA damage-response protein 53BP1 in human pancreatic cancer.
abstract: We have previously demonstrated that ultraviolet (UV) light is effective against a variety of cancer cells expressing fluorescent proteins in vivo as well as in vitro. In the present report, we compared the DNA damage repair (DDR) response of pancreatic cancer cells after UVB or UVC irradiation. The UV-induced DNA damage repair was imaged with green fluorescent protein (GFP) fused to the DDR-related chromatin-binding protein 53BP1 in MiaPaCa-2 human pancreatic cancer cells growing in 3D Gelfoam® histoculture and in superficial tumors grown in nude mice. 53BP1-GFP forms foci during DNA damage repair. A clonogenic assay in 2D monolayer culture initially showed that UVC and UVB inhibited MiaPaCa-2 cell proliferation in a dose-dependent manner, with UVC having more efficacy. Three-dimensional Gelfoam® histocultures and confocal imaging enabled 53BP1-GFP foci to be observed within 1 h after UV irradiation, indicating the onset of DDR response. UVB-induced 53BP1-GFP focus formation was observed up to a depth of 120 µm in MiaPaCa-2 cells on Gelfoam® compared to 80 µm for UVC. UVB-induced 53BP1-GFP focus formation was observed up to a depth of 80 µm in MiaPaCa-2 cells, implanted within skin flaps in mice, at a significantly greater extent than UVC. MiaPaCa-2 cells irradiated by UVB or UVC in the skin-flap mouse model had a significant decrease in tumor growth compared to untreated controls with UVB having more efficacy than UVC. Our results demonstrate that UVB has greater tissue penetration than UVC because of its longer wavelength and has clinical potential for eradicating superficial cancer.
authors.affiliation: AntiCancer, Inc., 7917 Ostrow Street, San Diego, California, 92111; Department of Surgery, University of California, 200 West Arbor Drive, San Diego, California, 92103; Department of Orthopedic Surgery, Graduate School of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa, 903-0125, Japan.
authors.forename: Fuminari
authors.initials: F
authors.lastname: Uehara
authors.forename: Shinji
authors.initials: S
authors.lastname: Miwa
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Tome
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Hiroshima
authors.forename: Shuya
authors.initials: S
authors.lastname: Yano
authors.forename: Mako
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Elena
authors.initials: E
authors.lastname: Efimova
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Matsumoto
authors.forename: Hiroki
authors.initials: H
authors.lastname: Maehara
authors.forename: Michael
authors.initials: M
authors.lastname: Bouvet
authors.forename: Fuminori
authors.initials: F
authors.lastname: Kanaya
authors.forename: Robert M
authors.initials: RM
authors.lastname: Hoffman
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000528:radiation effects; D004249:DNA Damage / Q000235:genetics / Q000528:radiation effects*; D004260:DNA Repair / Q000235:genetics / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000528:radiation effects; D051379:Mice; D008819:Mice, Nude; D008822:Mice, Transgenic; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000473:pathology / Q000532:radiotherapy*; D014183:Transplantation, Heterologous; D000071857:Tumor Suppressor p53-Binding Protein 1; D014466:Ultraviolet Rays; D014467:Ultraviolet Therapy / Q000379:methods*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C498301:TP53BP1 protein, human; D000071857:Tumor Suppressor p53-Binding Protein 1; D049452:Green Fluorescent Proteins
keywords: 53BP1; DNA DAMAGE; GFP; MiaPaCa-2; NUDE MICE; PANCREATIC CANCER; REPAIR RESPONSE; SKIN FLAP; THREE-DIMENSIONAL CULTURE GELFOAM® IMAGING; UVB; UVC