ARSENIC CONTAINING MIXTURES IN ANGIOSARCOMA INDUCTION

描述(申请人的描述)： 该项目将在科罗拉多州立大学山麓校区执行 温迪·A·波特的大学，D.V.M.波特博士的长期目标包括 整合病理学、毒理学和生物医学学科 在癌症研究领域的工程学。她的近期目标包括 调查三种常见地下水污染物的作用， 单独和联合，在肝血管肉瘤的发生发展中。 波特博士将遵循的研究职业发展计划包括 课程工作的跨学科背景和实践实施 在实验室和实验室中的知识和技能发展 数学建模领域。 本项目的长期目标是：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(1，2-DCE)- 与血管肉瘤的发展有关的致病因素；以及2) 将这些研究的数据用于生理学研究 药代动力学/药效学(PB-PK/PD)模型及统计学和 用于健康风险评估的数学建模技术 人物刻画。本项目的具体目标是：1)确定 砷单独作用在多大程度上会导致 血管肉瘤；2)评价协同致癌活性是否 当砷与氯乙烯和/或1，2-DCE结合时的结果；3) 建立单一化学品靶区组织剂量学PB-PK/PD模型 暴露于砷、氯乙烯、 和/或1，2-DCE；以及4)建立细胞周转和致癌模型 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1，2-二氯乙烷有关。这些 目标将通过使用中期血管肉瘤生物测定来实现 单独调查上述每种化学品的影响，并 联合用药诱导肝血管肉瘤。从这些网站收集的数据 实验将被用来开发模型来确定癌症风险和 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.