Miller Alexandra C, Rivas Rafael, Tesoro Leonard, Kovalenko Gregor, Kovaric Nikola, Pavlovic Peter, Brenner David
Science Research Department, Armed Forces Radiobiology Research Institute, Radiology and Radiation Sciences Department, Uniformed Services University of the Health Sciences, Bethesda, MD 20889, United States; Center for Radiological Research, Columbia University Medical Center, Columbia University, New York, NY 10022, United States; New York University, School of Medicine, 550 First Avenue, New York, NY 10016, United States.
Science Research Department, Armed Forces Radiobiology Research Institute, Radiology and Radiation Sciences Department, Uniformed Services University of the Health Sciences, Bethesda, MD 20889, United States.
Toxicol Appl Pharmacol. 2017 Sep 15;331:135-141. doi: 10.1016/j.taap.2017.06.004. Epub 2017 Jun 9.
Depleted uranium (DU) is a radioactive heavy metal used primarily in military applications. Published data from our laboratory have demonstrated that DU exposure in vitro to immortalized human osteoblast cells (HOS) is both neoplastically transforming and genotoxic. In vivo studies have also demonstrated that DU is leukemogenic and genotoxic. DU possesses both a radiological (alpha particle) and chemical (metal) component but is generally considered a chemical biohazard. Studies have shown that alpha particle radiation does play a role in DU's toxic effects. Evidence has accumulated that non-irradiated cells in the vicinity of irradiated cells can have a response to ionization events. The purpose of this study was to determine if these "bystander effects" play a role in DU's toxic and neoplastic effects using HOS cells. We investigated the bystander responses between DU-exposed cells and non-exposed cells by co-culturing the two equal populations. Decreased cell survival and increased neoplastic transformation were observed in the non-DU exposed cells following 4 or 24h co-culture. In contrast Ni (II)- or Cr(VI)- exposed cells were unable to alter those biological effects in non-Ni(II) or non-Cr(VI) exposed co-cultured cells. Transfer experiments using medium from the DU-exposed and non-exposed co-cultured cells was able to cause adverse biological responses in cells; these results demonstrated that a factor (s) is secreted into the co-culture medium which is involved in this DU-associated bystander effect. This novel effect of DU exposure could have implications for radiation risk and for health risk assessment associated with DU exposure.
贫铀(DU)是一种主要用于军事用途的放射性重金属。我们实验室发表的数据表明,体外将永生化人成骨细胞(HOS)暴露于贫铀会导致肿瘤转化和基因毒性。体内研究也表明,贫铀具有致白血病和基因毒性。贫铀具有放射性(α粒子)和化学(金属)成分,但通常被认为是一种化学生物危害。研究表明,α粒子辐射确实在贫铀的毒性作用中发挥作用。越来越多的证据表明,受辐射细胞附近的未受辐射细胞会对电离事件产生反应。本研究的目的是使用HOS细胞确定这些“旁观者效应”是否在贫铀的毒性和肿瘤效应中起作用。我们通过将两个相等数量的细胞共培养来研究贫铀暴露细胞和未暴露细胞之间的旁观者反应。共培养4或24小时后,未暴露于贫铀的细胞中观察到细胞存活率降低和肿瘤转化增加。相比之下,暴露于镍(II)或铬(VI)的细胞无法改变未暴露于镍(II)或铬(VI)的共培养细胞中的那些生物学效应。使用来自贫铀暴露和未暴露共培养细胞的培养基进行的转移实验能够在细胞中引起不良生物学反应;这些结果表明,一种因子被分泌到共培养基中,该因子与这种与贫铀相关的旁观者效应有关。贫铀暴露的这种新效应可能对辐射风险以及与贫铀暴露相关的健康风险评估产生影响。