STATISTICAL MODELS IN TOXICOLOGY AND BIOCHEMISTRY

这个项目旨在增加我们对使用和 数学和统计模型在毒理学和生物医学中的应用 生物化学和实施新的模型来帮助解释目前的 研究成果。这项研究工作探索了一系列不同的 生物学领域，包括致癌、药理学、发育 生物学、神经学和免疫学。在致癌方面；(1)发现 肿瘤发病率不能用来提供准确的 致癌机制；(2)对致癌能力的估计 针对生存中化学相关变化的调整被开发出来并正在 正在评估中；(3)致癌的数学模型 明确将DNA修复纳入多阶段过程 已开发并正在应用于 皮肤和肝脏模型；(4)2，3，7，8-TCDD和1，3-丁二烯两种化学物质， 正在探索作为应用基于机械的 用于估计致癌风险的数学模型；(5) 检测母乳中致癌物质的潜在缩短寿命作用 研究发现，只有母乳中的极端水平的污染物 比不能母乳喂养更危险；(6)形状 利用生物学信息绘制致癌剂量-效应曲线 对该化学物质的活性进行了研究，表明该化学物质 结构与剂量-反应形状有很好的相关性。在畸形学中，有几个 用于估计畸形风险的模型(例如，Rai和Van Ryzin模型) 评估了与现有数据的一致性，并且没有发现模型 对于这些目的来说是足够的。在免疫毒理学中，人们发现 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。 具有高致癌可能性的化合物。在神经学方面， NINDS正在进行一项研究，以应用多变量平滑 描述大脑区域和大脑区域之间关系的技术 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.