Non-cancer atherosclerotic effects associated with environmental and therapeutic radiation doses: The Chernobyl thyroid cancer children study

Abstract

The Chernobyl disaster, which took place on April 26th 1986 at the nuclear plant in northern Ukraine, represents the largest everhappened nuclear accident. About fivemillion people were exposed to radioactive contamination in Belarus, Russian Federation and Ukraine, with an estimated individual radiation dose ranging from few mSv to some hundred mSv [1]. The main health effect observed was an increase in the incidence of thyroid cancer in the young, but a number of non-cancer end points have been reported [2]. Recently, studies on the atomic bomb survivors in Japan demonstrated that moderate doses of ionizing radiations may contribute to excess cardiovascular disease risk [3], as confirmed also by a metaanalysis [4]. However, cardiovascular effects of low–moderate doses are still largely unexplored [5]. The aim of the present study was to assess the proatherosclerotic effects of radiation exposure in survivors of Chernobyl disaster, subsequently diagnosed with papillary thyroid cancer and treated with radioiodine ablation. Forty-six volunteers were enrolled: 23 subjects who were children (≤8 years old) living in the Chernobyl area in Belarus at the time of the nuclear blast in 1986 (group E-exposed), subsequently diagnosed and treated with radioiodine ablation for papillary thyroid cancer; 23 nonexposed (NE) healthy subjects, matched with E for age, gender and cardiovascular risk factors. All subjects underwent carotid intima–media thickness assessment (CIMT), aortic and carotid stiffnessmeasurement, andperipheral blood testing forEPCevaluation. In a subset of 28 subjects (14 subjects from each group), endothelial function was assessed by brachial artery flow-mediated dilation (FMD). A volume of 100 μL peripheral blood was immunostained with the following monoclonal antibodies: PERcP-conjugated human antiCD34, fluorescein-conjugated human anti-kinase insert domain receptor (KDR), human anti-CD133, or isotype control, and then analyzed by flow-cytometry. Carotid–femoral pulse wave velocity (PWV) was performed (SphygmoCor, AtCor Medical, Sydney, Australia) [6]. Common carotid artery ultrasound scans analyzed by means of Carotid Studio (Cardiovascular Suite; Quipu srl, Pisa, Italy), an algorithm for the automatic evaluation of the instantaneous carotid diameter, CIMT, distensibility coefficient and stiffness [7]. Non-invasive ultrasound assessment of brachial endothelial function was performed as previously described [6]. An automated system for real-time detection of brachial artery diameter by analysis of B-mode ultrasound image sequences was used (FMD Studio, Cardiovascular Suite: Quipu srl, Pisa, Italy). Endothelium-dependent dilation was induced by reactive hyperemia following a 5-min forearm cuff occlusion at 300 mm Hg. Endothelium-independent dilation was obtained by sublingual administration of 25 μg glyceryl-trinitrate (GTN). The baseline characteristics of the study participants are given in Table 1. In E mean total radiation dose was 47.3 ± 16.1 mCi (range 30–200 mCi). All E subjects were treated with L-thyroxin: their median TSH was 0.018 μg/mL (25–75 percentile: 0.007–0.462). Subpopulations of putative EPCs (CD34 + KDR+, CD34+ CD133+, CD34 + CD133 + KDR+) expressed as cell numbers per 10 cytometric events, were significantly decreased in E group when compared to NE group (Table 2, Fig. 1). E and NE presented similar carotid diameter, CIMT, distensibility and stiffness, as well as similar carotid–femoral PWV (Table 2). PP amplification from carotid to brachial site was significantly higher in E than in NE even after considering age, height and heart rate as covariates (P = 0.04). Carotid AIx was also higher in E than in NE (Table 2). E and NE showed similar brachial artery diameter, absolute and percent hyperemic change in diameter and shear rate, whereas in E response to GTN was significantly greater than in NE (Table 2). Themain result of this study is that in a group of young survivors of the Chernobyl nuclear disaster, subsequently treated with radioiodine ablation for thyroid cancer, the number of EPCs was significantly reduced in comparison to healthy volunteers, suggesting a reduced endothelial regeneration and repair capacity. This selective alteration, International Journal of Cardiology 168 (2013) 4255–4592