Effects of low-dose ionizing radiation and menadione, an inducer of oxidative stress, alone and in combination in a vertebrate embryo model.
Effects of low-dose ionizing radiation and menadione, an inducer of oxidative stress, alone and in combination in a vertebrate embryo model.
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DOI：
10.1667/rr3042.2
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发表时间：
2012-11
影响因子：
3.4
通讯作者：
Dynan WS
中科院分区：
文献类型：
--
作者：
Bladen CL;Kozlowski DJ;Dynan WS
先前的工作已经建立了斑马鱼胚胎作为研究暴露于低剂量电离辐射的生物效应的体内模型。辐射的已知效应之一是提高组织中活性氧（ROS）的水平。然而，ROS也作为正常代谢的副产物产生，并且无论来源如何，ROS对DNA产生类似的化学损伤。在这里，我们使用斑马鱼胚胎模型，以调查是否低剂量（0-1.5戈伊）辐射和内源性活性氧的影响是不同的机制。我们通过暴露于低浓度的醌类药物甲萘醌来增加内源性ROS的水平。对活胚胎的成像研究表明，暴露于3 μM或更高浓度的甲萘醌会显著增加ROS水平。这种治疗与生长延迟和形态异常相关，这些都是部分或完全可逆的。相比之下，暴露于低剂量的电离辐射对总体生长或形态没有明显影响，尽管TUNEL阳性凋亡细胞增加，与先前研究的结果一致。进一步的研究表明，辐射和甲萘醌暴露的联合效应大于单独使用任何一种药剂，并且Ku 80（一种对修复辐射诱导的DNA损伤很重要的基因）表达的减弱对甲萘醌敏感性只有轻微的影响。总之，结果表明，电离辐射和甲萘醌通过不同的机制影响胚胎。
Prior work has established the zebrafish embryo as an in vivo model for studying the biological effects of exposure to low doses of ionizing radiation. One of the known effects of radiation is to elevate the levels of reactive oxygen species (ROS) in tissue. However, ROS are also produced as byproducts of normal metabolism and, regardless of origin, ROS produce similar chemical damage to DNA. Here we use the zebrafish embryo model to investigate whether the effects of low-dose (0–1.5 Gy) radiation and endogenous ROS are mechanistically distinct. We increased levels of endogenous ROS by exposure to low concentrations of the quinone drug, menadione. Imaging studies in live embryos showed that exposure to 3 μM or higher concentrations of menadione dramatically increased ROS levels. This treatment was associated with a growth delay and morphologic abnormalities, which were partially or fully reversible. By contrast, exposure to low doses of ionizing radiation had no discernable effects on overall growth or morphology, although, there was an increase in TUNEL-positive apoptotic cells, consistent with the results of prior studies. Further studies showed that the combined effect of radiation and menadione exposure are greater than with either agent alone, and that attenuation of the expression of Ku80, a gene important for repair of radiation-induced DNA damage, had only a slight effect on menadione sensitivity. Together, results suggest that ionizing radiation and menadione affect the embryo by distinct mechanisms.