STATISTICAL MODELS IN TOXICOLOGY AND BIOCHEMISTRY

这个项目旨在增加我们对使用和 模型在毒理学和生物化学中的应用及实施新的 有助于解释当前研究成果的数学模型。这个 研究工作探索了不同的生物学领域，包括 癌症发生学、药理学、发育生物学和免疫学。在……里面 癌变的多阶段模型的充分性 评估未经治疗的动物的肿瘤发病率。另外， 来自动物实验的致癌效力的估计 因为与化学有关的生存变化已经被开发出来并正在被 已评估。一种显式的致癌数学模型 将DNA修复纳入正在开发的多阶段过程中。 允许我们使用该模型的数学细节已经开发出来了 目前的研究主要集中在使用数据来实现该模型 例如，化学品。在另一个研究领域，动物的设计 实验，致癌的克隆两阶段模型的意义 对设计的为期两年的啮齿动物生物测定进行了评价。一个简单的 使用年龄相关剂量方案的设计产生了独特的肿瘤模式 发病率，可以为致癌机制提供更好的信息。 这项研究还在继续，重点放在 致癌过程。我们还在研究致癌的形态 利用生物活性信息绘制剂量-反应曲线 化学药品。选择适当的形状(阈值或非阈值)对于 准确估计致癌风险。在畸形学中，有几个风险 评估模型与现有数据的一致性进行了评估。没有模特 被发现是足够的，有些被发现产生了误导性的结果。 畸形学的另一项努力涉及重采样技术的能力。 和准似然方法来解释落叶间的相关性。 对死亡率和发病率风险估计的补充研究 已经开始暴露在免疫抑制化学物质中。

This project is intended to increase our understanding of the use and application of models in toxicology and biochemistry and to implement new mathematical models to aid in explaining current research findings. The research effort explores a diverse range of biological areas including carcinogenesis, pharmacology, developmental biology and immunology. In carcinogenesis, the adequacy of the multistage model of carcinogenesis for estimating tumor incidence rates in untreated animals was evaluated. Also, an estimate of carcinogenic potency from animal experiments which adjusts for chemically related changes in survival has been developed and is being evaluated. A mathematical model of carcinogenesis which explicitly incorporates DNA repair into the multistage process is under development. The mathematical details allowing us to use the model have been developed and current research is focused on using data for implementing this model for example chemicals. In another research area, the design of animal experiments, the implications of a clonal two-stage model of carcinogenesis on the design of the two-year rodent bioassay was evaluated. A simple design using age-dependent dosing schemes produced unique patterns of tumor incidence which can provide better information on carcinogenic mechanism. This research is continuing with emphasis on the number of stages in the carcinogenesis process. We are also studying the shape of carcinogenesis dose-response curves using information on biological activity of the chemical . Choosing the proper shape (threshold or not) is critical to an accurate estimate of carcinogenic risk. In teratology, several risk assessment models were evaluated for agreement with existing data. No model was found to be adequate and some were found to produce misleading results. Another effort in teratology concerns the ability of resampling techniques and quasi-likelihood methods to account for interlitter correlations. Additional research into the estimation of risks of mortality and morbidity from exposure to immunosuppressive chemicals has begun.