Effects of cosmic radiation and microgravity on human dermal fibroblasts during the foton M3 mission

Skin deterioration is one of the major detrimental effects experienced by astronauts in space. The skin being the largest organ of the human body and serving as its protective shield is highly susceptible to harmful environmental influences. In order to understand the effects of space conditions on the human skin, it is important to unravel the underlying cellular mechanisms altered. For this purpose, the Foton M3 RADCELLS experiment focussed on the damaging effects of space radiation and microgravity on human dermal fibroblasts. The Foton M3 is a robotic spacecraft that flew at low orbit around the Earth for 12 days in September 2007. Within the Foton M3, samples were mounted into a biobox which was devised so that part of the samples experienced 0g whereas the other part resided in a 1g centrifuge as internal control. 3 cell types of human dermal fibroblast origin were tested: one wildtype (the human normal fibroblast cells (NHDFc)) and two human mutant fibroblast cells with impaired nuclear architecture (lamin knock-out and Hutchinson-Gilford Progeria patient). By the use of the multiplex array assay, culture supernatants of space and ground cultures were submitted to a thorough study of 89 proteins (chemokines, cytokines, interleukins, metalloproteinases, tumor markers) involved in inflammation, cancer development, metabolism and various cardiovascular processes. The results show variations in the chemokine concentrations in comparison with the ground control for pro-inflammatory cytokines, like IL-1 beta, TNF-beta and RANTES; for metalloproteinases associated with inflammation, like MMP-2, MMP-9 and TIMP-1; for a few tumoral agents (like CA 19-9) as well as for some hormones involved in metabolism like insuline. In conclusion, we show that cosmic radiations and microgravity differently affect the inflammation and tumorigenicity pathways. Furthermore, the three fibroblast cell types showed a different response to space conditions underlining the importance of nuclear organization in damage control and stress response. The current results therefore indicate that the individual and combined effects of cosmic radiation and microgravity involve complex interdependent biological mechanisms, particularly involved in the inflammation and in cancer development. This research is financially supported by a PRODEX/ESA contract (C90-303).