gms | German Medical Science

Objective: Ionizing radiation is a known risk factor for the possible transition of dura mater into a meningeal neoplasia. However, the effects of diagnostic and therapeutic radiation on this mechanism are still largely unknown. Nonetheless, the stem cell hypothesis is often used to explain tumorigenesis. The aim of this study was to investigate the effect of ionizing radiation on a possible reprogramming to the stem cell phenotype in primary dura mater cell cultures (DMC).

Methods: Three DMCs were exposed to a single photon radiation dose (1, 2, 4, 8, 12, 16, 20 Gy) and cultured under standard conditions until they reached the primary (10 passes) or secondary (84 days after irradiation) endpoint. Generation times, passenger ability and morphological abnormalities were analyzed. For the analysis of possible reprogramming effects, the expression of the transcription factor NANOG and its regulators SOX2 and OCT4 was determined by immunocytochemistry and qPCR compared to non-irradiated healthy cells.

Results: The analysis showed that especially in the irradiation groups 4 to 8 Gy higher generation times were observed compared to the control group not irradiated and thus slower or stagnating growth. Clear signs of necrotic processes were not detected. In parallel, the non-pathological cells irradiated with 4GY showed increased expression levels for NANOG (r=2.04) as well as OCT4 (r=2.14) and SOX2 (r= 1.17) and CD44 (r=1.68). The DMCs treated with 8Gy did not increase the expression levels of NANOG (r=0.55), SOX2 (r=0.25) and OCT4 (r=0.50) as well as CD44 (r=0.50).

Conclusion: The high expression values of the transcription factors NANOG, SOX2 and OCT4 as well as the stem cell marker CD44 clearly show that an induction of stem cell properties in non-pathological dura mater cells is possible, even after a single irradiation with a 4 Gy dose. Thus, it seems likely that ionizing radiation has long-term effects on reprogramming and thus on possible tumor initiating processes.