Picano et al. BMC Cancer 2012, 12:157 http://www.biomedcentral.com/1471-2407/12/157 Page 6 of 13 Figure 3 The modified cellular and pathophysiological model leading to neurodegenerative and atherosclerotic disease through possibly shared molecular pathways. Modified from ref. 48. factors leading to increased damage, genomic instability and cell aging, cell apoptosis, local necrosis, and altered blood flow [48] (Figure 3). Clinical laboratory data from the clinical Adult Health Study subset also provide some insight into subclinical changes underlying disease devel- opment, such as an increased amount of aortic arch calci- fication [49], dose-dependent increases in longitudinal trends for systolic and diastolic blood pressure [50], serum cholesterol levels [51], and dose-related increase in serum levels of various inflammation markers among the cohort subjects, including C-reactive protein, interleukin-6 and sialic acid [52], with decreases in proportion of CD4+ T- cells in the peripheral blood lymphocytes, suggesting a role of radiation-induced immunity in promotion of pre-clin- ical inflammation [53]. Radiation effects on the vascular system are not limited to macrovessels such as carotid arteries but may also in- volve small arterioles and microcirculatory function in vessels too small to be imaged by angiography [54,55]. It is now well-recognized that many of the same risk fac- tors that cause heart disease also can lead to vascular de- mentia in the elderly [56] and microvascular brain Figure 4 The cellular and experimental effects of x-ray on adult brain. Adult neurogenesis occurs in the caudate nucleus, hippocampus and olfactory bulb (left upper panel, A); environmental factors can positively (environmental enrichment) or negatively modulate adult brain plasticity (right upper panel, B); of many physical, chemical and genetic factors modulating plasticity, x-rays are a recognized potent inhibitor of neurogenesis (left lower panel, C). The inhibition of neurogenesis in a mouse model is more striking in males than in females, and with repetitive, chronic rather than with acute exposures (right lower panel, D, modified from ref 70, Silasi et al.).