Non-cancer diseases and non-targeted effects.

It is well established that moderate to high doses of radiation can increase the occurrence also of a variety of non-cancer effects in exposed individuals, but for radiation protection purposes it has generally been assumed that there is a threshold of dose below which no significant non-cancer effects (apart from hereditary disease) arise. In recent years, there is growing epidemiological evidence of excess risk of late occurring cardiovascular disease at much lower radiation doses and occurring over much longer intervals after radiation exposure without a clear cut threshold. However, the epidemiological evidence available so far for non-cancer health effects after exposure to moderate or low radiation doses is suggestive rather than persuasive. The mechanisms of radiation-induced vascular disease induction are far away from being understood. However, it seems to be very likely that inflammatory responses are involved. Recent experimental studies by Stewart et al. [25] could demonstrate that high dose exposure to the cardiovascular system is associated with an earlier onset and accelerated development of macrophage-rich, inflammatory atherosclerotic lesions prone to intra-plaque hemorrhage and may also cause a decrease in myocardial perfusion. Both, macro-vascular and micro-vascular radiation effects involve the endothelium and pro-inflammatory signalling cascades. If modulation of inflammatory response is arguably also the most likely cause of radiation-induced cardiovascular disease after low dose exposure, this also implies a role for non-targeted radiation effects. In the absence of a convincing mechanistic explanation of the currently available epidemiological evidence for radiation-induced cardiovascular risk at low radiation doses, caution is required in the interpretation of the statistical associations. On the other hand, the possibility of such a causal explanation cannot be reliably excluded. Further epidemiological and biological evidence from currently ongoing research projects will allow a firmer conclusion to be drawn.