Radiation-induced apoptosis in human lymphocytes : studies on expression, function and effects of different radiation qualities

Abstract: We are constantly exposed to radiation. Radiation causes damage to our cells. By the removal of damaged and unwanted cells, apoptosis is considered to be one of the most indispensable defence processes for a multi-cellular organism.To improve the knowledge and understanding of the expression and function of apoptosis in human cells exposed to radiation of different qualities, lymphocytes from healthy individuals and radiosensitive individuals suffering from ataxia telangiectasia (A-T) were studied. Studies on radiation-induced chromosomal aberrations (CA) in normal cells revealed that the expression of apoptosis significantly reduced the number of cells with CA after the first mitosis. For the induction of chromosomal instability observed after several cell divisions, neither a prolonged apoptotic expression time nor a lower genotoxic stress by low dose-rate (LDR) irradiation, seemed to influence the response.Further investigations on the effects of LDR exposure on apoptosis indicated a dose-rate effect, although not statistically verified. A prolonged post-irradiation time in G0-phase was shown to significantly increase the apoptotic response, which was efficiently counteracted by addition of growth factors.The apoptotic response was found to be significantly increased after exposure to high linear energy transfer (LET) radiation compared to low-LET. High-LET irradiation did not only increase the frequency of apoptotic cells, but did also induce a significantly faster apoptotic response, which revealed time-dependent relative biological effectiveness (RBE) values in the range of 1.3-3.0.In studies on the expression of radiation-induced apoptosis in A-T cells it was found that low-LET irradiation did neither induce apoptosis, G1-phase arrest nor enhanced levels of p53/p21 (WAF1) proteins. However, high-LET irradiation did induce apoptosis and G1-phase arrest in A-T cells, despite the absence of a p53/p21(WAF1) response.