The effect of low dose ionizing radiation on homeostasis andfunctional integrity in an organotypic human skin model

Outside the protection of Earth’s atmosphere, astronauts are exposed to low doses of high linear energy transfer (LET) radiation. Future NASA plans for deep space missions or a permanent settlement on the moon are limited by the health risks associated with space radiation exposures. There is a paucity of direct epidemiological data for low dose exposures to space radiation-relevant high LET ions. Health risk models are used to estimate the risk for such exposures, though these models are based on high dose experiments. There is increasing evidence, however, that low and high dose exposures result in different signaling events at the molecular level, and may involve different response mechanisms. Further, despite their low abundance, high LET particles have been identified as the major contributor to health risk during manned space flight. The human skin is exposed in every external radiation scenario, making it an ideal epithelial tissue model in which to study radiation-induced effects. Here, we exposed an in vitro three-dimensional (3-D) human organotypic skin tissue model to low doses of high LET oxygen (O), silicon (Si)and iron (Fe) ions. We measured proliferation and differentiation profiles in the skin tissue and examined the integrity of the skin’s barrier function. We discuss the role of secondary particles in changing the proportion of cells receiving a radiation dose, emphasizing the possible impact on radiation-induced health issues in astronauts.

ionizing radiation, EFT-400, keratin 10, filaggrin, EdU (thymidine analog), barrier disruption

linear energy transfer (LET) radiation, LET oxygen ions, LET silicon ions, LET iron ions, Lucifer yellow