title: Unusual prolongation of radiation-induced G2 arrest in tumor xenografts derived from HeLa cells.
abstract: The effect of ionizing radiation on cell cycle kinetics in solid tumors remains largely unknown because of technical limitations and these tumors' complicated structures. In this study, we analyzed intratumoral cell cycle kinetics after X-irradiation of tumor xenografts derived from HeLa cells expressing the fluorescent ubiquitination-based cell cycle indicator (Fucci), a novel system to visualize cell cycle kinetics in vivo. Cell cycle kinetics after X-irradiation was examined by using tumor sections and in vivo real-time imaging system in tumor xenografts derived from HeLa cells expressing Fucci. We found that G2 arrest was remarkably prolonged, up to 5 days after 10-Gy irradiation, in contrast to monolayer cultures where G2 arrest returned within 24 h. Cells isolated from tumors 5 days after irradiation exhibited a higher surviving fraction than those isolated immediately or one day after irradiation. In this study, we clearly demonstrated unusual post-irradiation cell cycle kinetics in tumor xenografts derived from HeLa-Fucci cells. Our findings imply that prolonged G2 arrest occurring in tumor microenvironments following irradiation may function as a radioresistance mechanism.
authors.affiliation: Section of Oral Radiation Oncology, Department of Oral Health Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kaida
authors.affiliation: Section of Oral Radiation Oncology, Department of Oral Health Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Miura
mesh_terms: D000818:Animals; D004249:DNA Damage; D059565:G2 Phase Cell Cycle Checkpoints / Q000528:radiation effects*; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011839:Radiation, Ionizing; D014183:Transplantation, Heterologous; D059016:Tumor Microenvironment / Q000528:radiation effects*
keywords: Fluorescent ubiquitination-based cell cycle indicator (Fucci); G2 arrest; ionizing radiation; live imaging; tumor microenvironments