The effects of depleted uranium shrapnel on mitochondrial cellular function.
贫铀弹片对线粒体细胞功能的影响。
基本信息
- 批准号:10201131
- 负责人:
- 金额:$ 42.73万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-05-21 至 2024-04-30
- 项目状态:已结题
- 来源:
- 关键词:AcuteAddressAdultAffectAfghanistanAnimalsAreaAwardBeta ParticleBiologicalCell Culture TechniquesCell physiologyChemicalsChronicCrista ampullarisCutaneousDNADNA DamageDataEmbryoEnvironmental ExposureExposure toFaceFishesGeneticGenome StabilityGoalsHealthHomeHumanImpairmentImplantIngestionInhalationInjuryIraqIsotopesLaboratoriesLarvaLongitudinal StudiesMalignant NeoplasmsMetabolismMetalsMethodsMilitary PersonnelMitochondriaMitochondrial DNAModernizationNative AmericansNative-BornNavajoNuclearNuclear WeaponOccupationalOccupational ExposureOrganismOutcomePersonsPhysiologicalPigmentsPlayPopulationProductionRadiationRadioactivityRadioisotopesReactive Oxygen SpeciesRelaxationResearchResearch ActivityResearch PersonnelRiskRodent ModelRoleRouteSTEM careerScienceSideSiteSkinSoilSoldierStudentsSun ExposureSystemTechniquesTestingTimeToxic effectToxicologyTribesUV Radiation ExposureUltraviolet RaysUncertaintyUnderrepresented PopulationsUnited StatesUraniumVeteransWarZebrafishbasecell injurycombatcontaminated watercostexperimental studyexposed human populationgenotoxicitygraduate studentimprovedin vivoinnovationinsightirradiationmitochondrial dysfunctionmultilevel analysisnext generationnovelparticlephotoactivationresponsesubcutaneousultravioletundergraduate studentwaterborneweaponswound
项目摘要
Project Abstract
A consequence of modern combat is exposure to depleted uranium through the use of uranium-containing
munitions. Understanding the effects of environmental or occupational exposure to depleted uranium is important
for protecting human health. Research in the area of uranium chemical toxicology has yielded mixed results,
raising uncertainty as to the risks of depleted uranium exposure and mechanisms of action. The research
proposed here will address depleted uranium chemical toxicity in vivo and the role ultraviolet radiation may play
in potentiating (or synergizing) uranium’s mechanisms of action. The central question being addressed is if
depleted uranium internalized through shrapnel or wound contamination causes persistent cellular and genetic
damage including mitochondrial dysfunction and DNA damage, both of which are observed in cancer states.
In addition to the critical biomedical science encompassed by this project, an overarching goal of R15 awards
is to involve students with all aspects of the proposed research activities to engage the next generation of STEM
investigators. Students will carry out experiments using zebrafish (embryos, larvae and adults), to test the
hypothesis that internalized depleted uranium, in amounts that are occupationally and environmentally-relevant,
disrupts mitochondrial function and genomic stability. We will also test the hypothesis that ultraviolet B-ray (UV-
B) radiation interact with DU leading to synergistically increased genotoxicity. Notably, humans exposed to
depleted uranium, particularly as a consequence of shrapnel, may carry the metal burden in or near their skin
where interaction with sun exposure (including UV-B) may occur.
Our studies leverage a pigment-free strain of zebrafish that enables longitudinal tracking of uranium implants,
as the animal’s skin is transparent as a larva and translucent as an adult. Our unique study system is tractable
for students as demonstrated by our preliminary data in which the great majority of data was produced by student
researchers in the PI’s laboratory group. Furthermore, the zebrafish is less costly than rodent models and
relatively easy to maintain, making longitudinal studies well within our capabilities.
Outcomes derived from these studies will provide evidence for or against uranium chemical toxicology from
acute or persistent exposure from multiple routes of internalization. We assert this is a comprehensive approach
to assess the risk depleted uranium poses to humans while addressing potential risk modifiers.
项目摘要
现代战争的一个后果是,通过使用含铀弹药,
军火了解环境或职业接触贫铀的影响很重要
保护人类健康。铀化学毒理学领域的研究结果好坏参半,
这增加了贫铀接触风险和作用机制的不确定性。研究
这里提出的建议将讨论贫铀在体内的化学毒性和紫外线辐射可能发挥的作用
增强(或协同)铀的作用机制。核心问题是,
通过弹片或伤口污染内化的贫铀,
损伤包括线粒体功能障碍和DNA损伤,这两者都在癌症状态中观察到。
除了该项目所涵盖的关键生物医学科学外,R15奖项的总体目标
是让学生参与拟议研究活动的各个方面,以吸引下一代STEM
investigators.学生们将使用斑马鱼(胚胎,幼虫和成虫)进行实验,以测试
假设内部贫化铀的数量与职业和环境有关,
破坏线粒体功能和基因组稳定性。我们还将测试紫外线B射线(UV-
B)辐射与DU相互作用,导致协同增加遗传毒性。值得注意的是,
贫铀弹,特别是弹片造成的贫铀弹,可能将金属负荷带入或靠近其皮肤
其中可能发生与阳光照射(包括UV-B)的相互作用。
我们的研究利用了一种无色素的斑马鱼,可以纵向跟踪铀植入物,
因为这种动物的皮肤在幼虫时是透明的,在成虫时是半透明的。我们独特的学习系统是易于处理的
正如我们的初步数据所证明的那样,大部分数据是由学生产生的。
PI实验室的研究人员。此外,斑马鱼的成本低于啮齿动物模型,
相对容易维护,使纵向研究在我们的能力范围内。
从这些研究中得出的结果将提供支持或反对铀化学毒理学的证据,
急性或持续暴露于多种内化途径。我们认为这是一个全面的办法
评估贫铀对人类构成的风险,同时处理潜在的风险修正因素。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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{{ truncateString('Matthew Salanga', 18)}}的其他基金
The effects of depleted uranium shrapnel on mitochondrial cellular function, administrative diversity supplement
贫铀弹片对线粒体细胞功能的影响,行政多样性补充
- 批准号:
10473374 - 财政年份:2022
- 资助金额:
$ 42.73万 - 项目类别:
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