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Mechanism of turnover or persistence of radiation-induced myofibroblast in vitro.
Shimura, Tsutomu; Ando, Takahito; Narao, Momoka; Sasatani, Megumi; Kamiya, Kenji; Ushiyama, Akira.
Afiliação
  • Shimura T; Department of Environmental Health, National Institute of Public Health , Saitama, Japan.
  • Ando T; Department of Hygienic Chemistry , Meiji Pharmaceutical University , Tokyo, Japan.
  • Narao M; Department of Hygienic Chemistry , Meiji Pharmaceutical University , Tokyo, Japan.
  • Sasatani M; Department of Experimental Oncology, Research Center for Radiation Genome Medicine, Research Institute for Radiation Biology and Medicine (RIRBM), Hiroshima University , Hiroshima, Japan.
  • Kamiya K; Department of Experimental Oncology, Research Center for Radiation Genome Medicine, Research Institute for Radiation Biology and Medicine (RIRBM), Hiroshima University , Hiroshima, Japan.
  • Ushiyama A; Department of Environmental Health, National Institute of Public Health , Saitama, Japan.
Cell Cycle ; 19(23): 3375-3385, 2020 12.
Article em En | MEDLINE | ID: mdl-33225802
ABSTRACT
We recently made an important discovery that radiation induces myofibroblasts, which play a role in radiation-related carcinogenesis via tumor microenvironment formation. Here, we investigated the threshold dose and the mechanisms of myofibroblast induction to assess adverse radiation effects on normal cells. Single-dose of healthy human fibroblasts in vitro promotes myofibroblast induction at high doses (≥ 5 Gy). In contrast, repeated low dose of fractionated radiation is at least equivalent to high-dose single radiation regarding myofibroblast induction. ROS play a pivotal role in the process of myofibroblast induction in normal tissue injury. Antioxidants, such as epicatechin and ascorbic acid can prevent myofibroblast induction by scavenging ROS. We further investigated the role of DNA damage responses (DDR) on myofibroblast induction. Blocking the DDR using DNA-PK or AKT inhibitors enhanced cellular sensitivity to radiation and facilitated myofibroblast induction, whereas an ATM inhibitor also enhanced radiation sensitivity but abrogated ROS accumulation and myofibroblast induction. In contrast to standard culture conditions, myofibroblasts remained after low or moderate doses of radiation (below 2.5 Gy) under growth-restricted conditions. In conclusion, the recovery of damaged cells from radiation is essential for myofibroblast clearance, which restores stromal cell dormancy and prevents tumor microenvironment formation. However, residual ROS, by way of sustaining myofibroblast presence, can facilitate tumor microenvironment formation. Targeting ROS using antioxidants is effective in the mitigation of radiation-related adverse effects, such as growth retardation and myofibroblast induction, and helps protect normal tissues.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Doses de Radiação / Miofibroblastos Limite: Humans Idioma: En Revista: Cell Cycle Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Japão

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Doses de Radiação / Miofibroblastos Limite: Humans Idioma: En Revista: Cell Cycle Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Japão