ARSENIC CONTAINING MIXTURES IN ANGIOSARCOMA INDUCTION

描述（申请人描述）： 该项目将在科罗拉多州立大学的山麓校区执行 大学由Wendy A.波特，D.V.M.波特博士的长期目标包括 结合病理学、毒理学和生物医学学科， 癌症研究领域的工程学。 她的近期目标包括 调查三种常见的地下水污染物的作用， 单独和联合使用在肝血管肉瘤的发生中。 Pott博士将遵循的研究职业发展计划包括 课程的跨学科背景和实际实施 知识和技能的发展，在实验室和 数学建模竞技场。 该项目的长期目标是：1）评估致癌物质 亚慢性暴露于三种常见地下水的影响 污染物-砷、氯乙烯和1，2-二氯乙烷- 与血管肉瘤的发展有关的病原体;和2） 使用这些研究的数据， 药代动力学/药效学（PB-PK/PD）模型以及统计和 健康风险数学模型技术 特征化 该项目的具体目标是：1）确定 砷在多大程度上单独起作用， 血管肉瘤; 2）评估协同致癌活性是否可能 当砷与氯乙烯和/或1，2-DCE结合时的结果; 3） 开发PB-PK/PD模型，用于单一化学品的靶组织剂量测定， 暴露于砷，氯乙烯， 和/或1，2-DCE;和4）开发细胞更新和致癌模型 并将其与PB-PK/PD模型相结合，以表征癌症风险 与接触砷、氯乙烯和/或1，2-DCE有关。 这些 将使用中期血管肉瘤生物测定来实现目标， 单独研究上述每种化学品的影响， 联合诱导肝血管肉瘤。 从这些收集的数据 实验将用于开发模型，以确定癌症风险， 这些化学物质的安全饮用水水平。

DESCRIPTION (Applicant's Description): This project will be executed at the Foothills Campus of Colorado State University by Wendy A. Pott, D.V.M. Dr. Pott's long-term goals involve integrating the disciplines of pathology, toxicology and biomedical engineering in the realm of cancer research. Her immediate goals involve investigating the roles of three common groundwater contaminants, individually and in combination, in the development of hepatic angiosarcoma. The research career development plan Dr. Pott will follow involves an interdisciplinary background of coursework and practical implementation of knowledge and development of skills in the laboratory and in the mathematical modelling arena. The long-term objectives of this project are 1) to evaluate the carcinogenic effects of sub-chronic exposure to three common groundwater contaminants-arsenic, vinyl chloride and 1,2-dichloroethane (1,2-DCE) - implicated as etiologic agents in the development of angiosarcoma; and 2) to use data from these studies with physiologically-based pharmacokinetic/pharmacodynamic (PB-PK/PD) models and statistical and mathematical modelling techniques for the purpose of health risk characterization. The specific aims of this project are 1) to determine the extent to which arsenic alone will act to induce the development of angiosarcoma; 2) to evaluate whether synergistic carcinogenic activity may result when arsenic is combined with vinyl chloride and/or 1,2-DCE; 3) to develop PB-PK/PD models for target tissue dosimetry of single chemicals and combinations of chemicals following exposure to arsenic, vinyl chloride, and/or 1,2-DCE; and 4) to develop cell turnover and carcinogenesis models and integrate them with PB-PK/PD models to characterize cancer risks associated with exposure to arsenic, vinyl chloride and/or 1,2-DCE. These goals will be accomplished using a medium-term angiosarcoma bioassay to investigate the effects of each of the above-mentioned chemicals alone and in combination in inducing hepatic angiosarcoma. Data gathered from these experiments will be used to develop models to determine cancer risks and safe drinking water levels of these chemicals.