Belyakov1,2, O.V., Mitchell1, S.A., Parikh3, D., Randers-Pehrson1, G., Marino1, S.A., Amundson1, S.A., Geard1, C.R. and Brenner1, D.J. 1Center for Radiological Research, Columbia University, New York, NY 10032; 2Radiation Biology Laboratory, Research and Environmental Surveillance, Radiation and Nuclear Safety Authority, P.O. Box 14, FIN-00881, Helsinki, Finland; and 3Stuyvesant High School, New York, NY 10282.

This study by researchers at Columbia University’s Center for Radiological Research, Finland’s Radiation and Nuclear Safety Authority, and New York City’s Stuyvesant High School demonstrated how MatTek’s EpiDerm in vitro human skin tissue equivalent and EpiDermFT full-thickness in vitro human skin tissue equivalent can be used in vitro to study “bystander effects” of ionizing radiation on human skin tissue. Click on the following link for an overview of the radiation-induced bystander effect research being conducted at the Columbia University Radiological Research Accelerator Facility (RARAF) using MatTek’s EpiDerm and EpiDermFT in vitro 3-D human skin tissue equivalents (scroll down to “3D Tissue Systems” section): 3D Microbeam Studies in vitro. A central tenet in understanding the biological effects of ionizing radiation has been that the initially affected cells were directly damaged by the radiation. By contrast, evidence has emerged concerning ‘‘bystander’’ responses involving damage to nearby cells that were not themselves directly traversed by the radiation. These long-range effects are of interest both mechanistically and for assessing risks from low-dose exposures, where only a small proportion of cells are directly hit. Bystander effects have been observed largely by using single-cell in vitro systems that do not have realistic multicellular morphology; no studies have as yet been reported in three-dimensional, normal human tissue. Given that the bystander phenomenon must involve cell-to-cell interactions, the relevance of such single-cell in vitro studies is questionable, and thus the significance of bystander responses for human health has remained unclear. Here, researchers at Columbia University’s Center for Radiological Research, Finland’s Radiation and Nuclear Safety Authority, and New York City’s Stuyvesant High School describe bystander responses in EpiDerm, a three-dimensional, normal human-tissue system. Endpoints were induction of micronucleated and apoptotic cells. A charged-particle microbeam was used, allowing irradiation of cells in defined locations in the tissue yet guaranteeing that no cells located more than a few micrometers away receive any radiation exposure. Unirradiated cells up to 1 mm distant from irradiated cells showed a significant enhancement in effect over background, with an average increase in effect of 1.7-fold for micronuclei and 2.8-fold for apoptosis. The surprisingly long range of bystander signals in human tissue suggests that bystander responses may be important in extrapolating radiation risk estimates from epidemiologically accessible doses down to very low doses where non-hit bystander cells will predominate.


Alpha particles, Apoptotic cells, Bystander effects, EFT-300, EPI-200, EpiDerm, EpiDerm-FT, EpiDermFT, Full thickness skin model, Ionizing, Irradiation, Lipid profiles, Metabolically active, Microbeam Irradiation, Mitotically active, Normal human tissue, Radiation, Radiological risk

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