STATISTICAL MODELS IN TOXICOLOGY AND BIOCHEMISTRY

该项目旨在增加我们对使用的理解， 数学和统计模型在毒理学中的应用 生物化学和实施新的模型，以帮助解释目前的 研究结果。 研究工作探索了各种各样的 生物学领域，包括致癌作用、药理学、发育 生物学、神经学和免疫学。 在致癌作用中;（1）发现 肿瘤发病率不能用来提供准确的估计， 致癌机制;（2）致癌效力的估计， 调整化学相关的生存变化， （3）致癌作用的数学模型， 明确地将DNA修复纳入多阶段过程， 开发并正在应用于启动促进实验中， 皮肤和肝脏模型;（4）两种化学品，2，3，7，8-TCDD和1，3-丁二烯， 正在探索的例子，为应用机械为基础的 致癌风险评估的数学模型;（5）在 研究母乳中致癌物质对寿命缩短的潜在影响 研究发现，只有母乳中的污染物含量极高， 代表比母乳喂养失败更危险;（6）形状 利用生物信息的致癌剂量-反应曲线 化学活性的研究表明，化学 结构与剂量反应形状良好相关。 在畸形学中， 模型（例如，Rai和货车Ryzin模型估计畸形风险 评估了与现有数据的一致性，未发现模型 足以达到这些目的。 在免疫毒理学中，发现 免疫毒性和致突变性之间几乎没有关系 但致癌性和免疫毒性与免疫毒性有关 致癌性很高的化合物。 在神经学中， 一项与NINDS一起进行的研究工作正在进行中，以应用多元平滑 技术来描述大脑区域之间的关系， 身体的不同部位。

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 new models to aid in explaining current research findings. The research effort explores a diverse range of biological areas including carcinogenesis, pharmacology, developmental biology, neurology and immunology. In carcinogenesis; (1) it was found that tumor incidence rates cannot be used to provide accurate estimates of carcinogenic mechanism; (2) an estimate of carcinogenic potency which adjusts for chemically related changes in survival was developed and is being evaluated; (3) a mathematical model of carcinogenesis which explicitly incorporates DNA repair into the multistage process was developed and is being applied to initiation-promotion experiments in the skin and liver models; (4) two chemicals, 2,3,7,8-TCDD and 1,3-butadiene, are being explored as examples for the application of mechanistically-based mathematical models to the estimation of carcinogenic risks; (5) in examining potential life-shortening effects of carcinogens in breast milk it was found that only extreme levels of contaminants in breast milk represent more of a hazard than failure to breast feed; (6) the shape of the carcinogenesis dose-response curve using information on biological activity of the chemical has been studied and suggests that chemical structure correlates well with dose-response shape. In teratology, several models (e.g., Rai and Van Ryzin model) for estimating teratological risks were evaluated for agreement with existing data and no model was found to be adequate for these purposes. In immunotoxicology, it was found that there is little or no relationship between immunotoxicity and mutagenicity but that carcinogenicity and immunotoxicity are related with immunotoxic compounds having a high probability of being carcinogenic. In neurology, a research effort is underway with NINDS to apply multivariate smoothing techniques to characterize the relationship between areas of the brain and different parts of the body.