Skin Models at RARAF
We have used a variety of artificial tissue models (Mattek.com) in our investigation of radiation responses especially the bystander effect. Artificial skin tissues that have been used include EPI-200 that is a highly differentiated model of the human epidermis and EFT-300 which is a full thickness skin model. EPI-200 consists of normal, human-derived epidermal keratinocytes (NHEK) which have been cultured to form a multilayered, highly differentiated model of the human epidermis (7-10 cell layers, 75-100 μm thick). In addition to the epidermis, full thickness tissues contain normal, human-derived dermal Fibroblasts which have been cultured to form a multilayered, highly differentiated model of the human dermis and epidermis (700 μm thick).
Microbeam irradiation of these tissues has demonstrated bystander responses, as seen by micronuclei and apoptosis, as much as 1 mm away from the site of irradiation (Belyakov et. al. PNAS 102, 14203-8 2005). These tissues have also been used to demonstrate the activation of cellular signaling pathways, specifically those involving MAP kinases, in bystander tissues sections.
Belyakov O.V., Mitchell S.A., Parikh D., Randers-Pehrson G., Marino S.A., Amundson S.A., Geard C.R. and Brenner D.J. Biological effects in unirradiated human tissue induced by radiation damage up to 1 mm away. Proc Natl Acad Sci U S A 102:14203-14208 (2005). [abstract]