Bonassi Stefano, Cellai Filippo, Munnia Armelle, Ugolini Donatella, Cristaudo Alfonso, Neri Monica, Milić Mirta, Bonotti Alessandra, Giese Roger W, Peluso Marco E M
Clinical and Molecular Epidemiology, IRCCS San Raffaele Pisana, Rome, Italy; Department of Human Sciences and Quality of Life Promotion, San Raffaele University, Rome, Italy.
Cancer Risk Factor Branch, Regional Cancer Prevention Laboratory, ISPO-Cancer Prevention and Research Institute, Florence, Italy.
Toxicol Lett. 2017 Mar 15;270:1-7. doi: 10.1016/j.toxlet.2017.02.008. Epub 2017 Feb 7.
Asbestos is the commercial name for a group of silicate minerals naturally occurring in the environment and widely used in the industry. Asbestos exposure has been associated with pulmonary fibrosis, mesothelioma, and malignancies, which may appear after a period of latency of 20-40 years. Mechanisms involved in the carcinogenic effects of asbestos are still not fully elucidated, although the oxidative stress theory suggests that phagocytic cells produce large amounts of reactive oxygen species, due to their inability to digest asbestos fiber. We have conducted a mechanistic study to evaluate the association between 3-(2-deoxy-β-d-erythro-pentafuranosyl)pyrimido[1,2-α]purin-10(3H)-one deoxyguanosine (MdG) adducts, a biomarker of oxidative stress and lipid peroxidation, and asbestos exposure in the peripheral blood of 327 subjects living in Tuscany and Liguria, Italy, stratified by occupational exposure to asbestos. Adduct frequency was significantly greater into exposed subjects with respect to the controls. MdG per 10 normal nucleotides were 4.0±0.5 (SE) in 156 asbestos workers, employed in mechanic, naval, petrochemical, building industries, and in pottery and ceramic plants, versus a value of 2.3±0.1 (SE) in 171 controls (p<0.001). After stratification for occupational history, the effects persisted in 54 current asbestos workers, mainly employed in building renovation industry (2.9±0.3 (SE)), and in 102 former asbestos workers (4.5±0.7 (SE)), with p-values of 0.033, and <0.001, respectively. A significant effect of smoking on heavy smokers was found (p=0.005). Our study gives additional support to the oxidative stress theory, where MdG may reflect an additional potential mechanism of asbestos-induced toxicity.
石棉是一组天然存在于环境中并在工业中广泛使用的硅酸盐矿物的商业名称。接触石棉与肺纤维化、间皮瘤和恶性肿瘤有关,这些疾病可能在20至40年的潜伏期后出现。尽管氧化应激理论认为吞噬细胞由于无法消化石棉纤维而产生大量活性氧,但石棉致癌作用所涉及的机制仍未完全阐明。我们进行了一项机制研究,以评估3-(2-脱氧-β-D-赤藓糖基)嘧啶并[1,2-α]嘌呤-10(3H)-酮脱氧鸟苷(MdG)加合物(一种氧化应激和脂质过氧化的生物标志物)与意大利托斯卡纳和利古里亚地区327名居民外周血中石棉暴露之间的关联,并按职业性石棉暴露进行分层。与对照组相比,暴露组的加合物频率显著更高。156名石棉工人(受雇于机械、海军、石化、建筑行业以及陶器和陶瓷厂)每10个正常核苷酸中的MdG为4.0±0.5(标准误),而171名对照组为2.3±0.1(标准误)(p<0.001)。按职业史分层后,这种影响在54名主要受雇于建筑翻新行业的当前石棉工人(2.9±0.3(标准误))和102名以前的石棉工人(4.5±0.7(标准误))中仍然存在,p值分别为0.033和<0.001。发现吸烟对重度吸烟者有显著影响(p=0.005)。我们的研究为氧化应激理论提供了额外支持,其中MdG可能反映了石棉诱导毒性的另一种潜在机制。