Statistical Models In Toxicology And Biochemistry

毒理学和生物化学的统计模型

• 批准号: 6543018
• 负责人: Christopher J Portier
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6543018
• 关键词: biochemistry; cancer risk; cell cycle; chemical carcinogen; chemical carcinogenesis; dioxins; endocrinology; environmental contamination; environmental exposure; environmental toxicology; growth /development; immunology; laboratory rat; mathematical model; model design /development; neurology; pharmacology; statistics /biometry; thyroid hormones; vital statistics

Summary of Work: This project is intended to increase our understanding of the use and application of mathematical and statistical models in toxicology and biochemistry and to implement these mathematical models to aid in explaining current research findings. The research effort explores a diverse range of biological areas, including carcinogenesis, pharmacology, developmental biology, neurology, immunology and endocrinology. Major accomplishments include (1) A comprehensive, biologically based mathematical model was developed for the rat estrus cycle (2) A model was developed which describes the important factors for priming hepatocytes to enter the G1 phase of the cell cycle (3) A biologically-based model was developed for developmental toxicity (4) Data on morbidity for the city of Atlanta from 1980 to 1994 were analyzed to determine the effects of daily temperatures and air pollutant concentrations (NO2, O3 and PM10) on heat stress and related diseases (5) The impact of polymorphisms on the estimation of risks in a general population were explored (6) developed methods for evaluating the adequacy of benchmark doses, (7) began the development of methods to evaluate toxicogenomics data, (8) continued to aid in the scientific improvement of risk assessment methods through the application of sound science to key environmental issues such as exposure to TCDD, aflatoxins and endocrine disruptors.

工作总结：这个项目旨在增加我们对数学和统计模型在毒理学和生物化学中的使用和应用的理解，并实施这些数学模型来帮助解释当前的研究结果。这项研究探索了不同的生物学领域，包括癌症发生学、药理学、发育生物学、神经学、免疫学和内分泌学。主要成果包括：(1)建立了一个全面的、基于生物学的大鼠发情周期数学模型(2)开发了一个描述启动肝细胞进入细胞周期G1期的重要因素的模型(3)开发了一个基于生物学的发育毒性模型(4)分析了1980-1994年亚特兰大市的发病率数据，以确定每日温度和空气污染物浓度(NO2、O3和PM10)对热应激和相关疾病的影响(5)探讨了多态对普通人群风险估计的影响(6)开发了评估基准剂量充分性的方法，(7)开始制定评估毒物基因组学数据的方法，(8)继续通过将健全的科学应用于接触TCDD、黄曲霉毒素和内分泌干扰物等关键环境问题，协助改进风险评估方法。