Linear energy transfer dependent expression of putative radiation responsive genes in human cells

Abstract

Manned space travel is one of the main challenges of modern mankind, although the risk of exposure to radiation in space still remains a limiting factor. To estimate the risk of astronauts to develop cancer, molecular mechanisms of the cellular radiation response have to be analyzed. This thesis deals especially with the correlation between quality of radiation in terms of linear energy transfer (LET) and the consequential expression of radiation responsive genes in human embryonic kidney cells (HEK). Besides, factors like cellular survival, cell cycle progression and activation of the transcription factor Nuclear Factor κB (NF-κB) after exposure to radiation with LET ranging from 3 keV/μm (X-rays) to 9674 keV/μm (accelerated heavy ions, in this case Pb-208 ions) were investigated. Survival declined and NF-κB activation increased intensively with rising radiation dose, while a high LET always correlated with a strong response. A significant cell cycle arrest in the G 2 phase indicated active DNA repair, which was observed especially in medium LET range. In contrast, expression levels of radiation responsive genes (GADD45α, GADD45β, NFKBIA, p21) were proven to be higher after high LET irradiation. Some genes (HSF1, UNG, XRCC5) even responded only to high LET radiation. This indicates a dependency of the quality and intensity of cellular radiation response on LET.