Oncogenic bystander radiation effects in Patched heterozygous mouse cerebellum
| Autor: | Anna Saran, Simona Leonardi, M P Toni, Emanuela Pasquali, Simonetta Pazzaglia, Vincenzo Di Majo, Maria Pimpinella, Mariateresa Mancuso, S. Rebessi, Vincenzo Covelli, Mirella Tanori |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Patched Receptors
Patched Heterozygote Cell signaling DNA damage Receptors Cell Surface Cell Communication Biology Mice In vivo Cerebellum Neoplasms Radiation Ionizing Bystander effect Animals Genes Tumor Suppressor Epigenetics Multidisciplinary Gap Junctions Bystander Effect Biological Sciences Patched-1 Receptor Animals Newborn PTCH1 Immunology Cancer research DNA Damage |
| Zdroj: | Proceedings of the National Academy of Sciences. 105:12445-12450 |
| ISSN: | 1091-6490 0027-8424 |
| Popis: | The central dogma of radiation biology, that biological effects of ionizing radiation are a direct consequence of DNA damage occurring in irradiated cells, has been challenged by observations that genetic/epigenetic changes occur in unexposed “bystander cells” neighboring directly-hit cells, due to cell-to-cell communication or soluble factors released by irradiated cells. To date, the vast majority of these effects are described in cell-culture systems, while in vivo validation and assessment of biological consequences within an organism remain uncertain. Here, we describe the neonatal mouse cerebellum as an accurate in vivo model to detect, quantify, and mechanistically dissect radiation-bystander responses. DNA double-strand breaks and apoptotic cell death were induced in bystander cerebellum in vivo . Accompanying these genetic events, we report bystander-related tumor induction in cerebellum of radiosensitive Patched-1 ( Ptch1 ) heterozygous mice after x-ray exposure of the remainder of the body. We further show that genetic damage is a critical component of in vivo oncogenic bystander responses, and provide evidence supporting the role of gap-junctional intercellular communication (GJIC) in transmission of bystander signals in the central nervous system (CNS). These results represent the first proof-of-principle that bystander effects are factual in vivo events with carcinogenic potential, and implicate the need for re-evaluation of approaches currently used to estimate radiation-associated health risks. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|