Monte Carlo-Modelled Dose Calibration Curves for use in Modernized Biodosimetry
用于现代化生物剂量测定的蒙特卡罗模型剂量校准曲线
基本信息
- 批准号:RGPIN-2022-04931
- 负责人:
- 金额:$ 2.11万
- 依托单位:
- 依托单位国家:加拿大
- 项目类别:Discovery Grants Program - Individual
- 财政年份:2022
- 资助国家:加拿大
- 起止时间:2022-01-01 至 2023-12-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Biodosimetry (BD) is a tool for assessing the dose of ionizing radiation (IR) to which someone has been exposed. In order to understand the biological effects of this exposure, accurate physical dosimetry is required. Dose-response calibration curves (CC) are generated by irradiating blood samples with known doses and measuring the biological damage from each dose. This approach hinges on having well-calibrated physical dosimetry and methods to assess biological damage. Existing experimental methods measuring DNA damage from exposure to IR are well-established, but are slow and expensive. Currently the most sensitive of the assays has a lower limit of detection around 100 mSv. These methods need to be modernized to be specific to IR, to have excellent sensitivity to measure accurately and at lower doses and to be rapid for higher sample throughput. Monte Carlo (MC) modelling is a tool that can be used to simulate various radiation track structures and their implications for DNA damage including the resulting chromosomal geometry and aberrations. Software such as TOPAS-nBio provides a powerful toolkit to investigate radiation biology at sub-cellular scales and has greatly advanced this field of research. Accurate and informed BD requires CC that are representative of specific exposure scenarios of interest, including the relevant dose range, dose rate, and radiation type and quality. The long-term goals of this proposed research program are to (1) modernize BD methods using novel technologies and (2) establish validated, MC-based methods to model CC that could be transformed according to the exposure scenario. These modelled CC would be cost-effective, and would allow for more complex exposure scenarios such as protracted dose-rates and mixed beam exposures. Over the next five years, the short-term goals are to: (1) establish a validated MC model for DNA damage in blood cells, (2) validate a modelled CC for translocations as measured by FISH from X-ray exposures, (3) estimate a proof-of-concept dose for astronaut BD based on a space equivalent dose, and (4) model biological damage in the low dose regions (less than 100 mSv) to extrapolate CC. This work would take place in a government research laboratory at Health Canada (HC). Regarding feasibility of the proposed project, the necessary equipment is readily available and accessible for use. Furthermore, we are well-connected through collaborations to access other resources and centers of expertise as needed. HC has policies in place prioritizing healthy working environments, and promoting diversity and inclusivity in all aspects of our work. The funds requested would support this research program by focusing on the recruitment and training of highly qualified personnel. These results would help to understand the DNA damage mechanism from different radiation qualities at biologically relevant doses for both the space environment and the low-dose research programs.
生物剂量学(BD)是一种评估电离辐射(IR)剂量的工具。为了了解这种暴露的生物效应,需要精确的物理剂量测定。剂量-反应校准曲线(CC)是通过用已知剂量照射血液样本并测量每个剂量的生物损伤而产生的。这种方法取决于校准良好的物理剂量学和评估生物损伤的方法。现有的实验方法测量暴露在红外下的DNA损伤是完善的,但速度慢且昂贵。目前,最灵敏的测定法的检测下限约为100毫西弗。这些方法需要现代化,以特定于IR,具有优异的灵敏度,以准确和低剂量测量,并快速,以获得更高的样品通量。蒙特卡罗(MC)建模是一种工具,可用于模拟各种辐射轨道结构及其对DNA损伤的影响,包括由此产生的染色体几何形状和畸变。像TOPAS-nBio这样的软件提供了一个强大的工具包来研究亚细胞尺度的辐射生物学,并极大地推进了这一领域的研究。准确和知情的BD要求CC代表感兴趣的特定暴露情景,包括相关剂量范围、剂量率、辐射类型和质量。该研究计划的长期目标是:(1)使用新技术实现生物多样性方法的现代化;(2)建立经过验证的、基于生物多样性的方法来模拟可根据暴露情景进行转换的生物多样性。这些模拟的CC将具有成本效益,并将允许更复杂的暴露情景,如长期剂量率和混合光束暴露。未来五年,短期目标是:(1)建立验证MC模型血液细胞的DNA损伤,(2)验证建模CC易位以鱼的x射线曝光,(3)估计概念验证剂量基于太空的宇航员BD等效剂量,和(4)模型低剂量生物损伤区域(少于100 mSv)推断CC。这项工作将在加拿大政府研究实验室卫生(HC)。关于拟议项目的可行性,必要的设备是现成的,可供使用。此外,我们还通过合作建立了良好的联系,以便根据需要访问其他资源和专业知识中心。HC制定了政策,优先考虑健康的工作环境,并在我们工作的各个方面促进多样性和包容性。所要求的资金将通过集中征聘和培训高素质人员来支持这一研究计划。这些结果将有助于了解空间环境和低剂量研究项目在生物相关剂量下不同辐射质量对DNA的损伤机制。
项目成果
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{{ truncateString('Beaton, Lindsay', 18)}}的其他基金
Monte Carlo-Modelled Dose Calibration Curves for use in Modernized Biodosimetry
用于现代化生物剂量测定的蒙特卡罗模型剂量校准曲线
- 批准号:
DGECR-2022-00134 - 财政年份:2022
- 资助金额:
$ 2.11万 - 项目类别:
Discovery Launch Supplement
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