DERMAL ABSORPTION ENHANCERS AFFECT ORGANOTROPISM

皮肤吸收促进剂影响器官趋向性

• 批准号: 6128841
• 负责人: Glenn Talaska
• 金额: $ 24.66万
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-30 至 2002-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6128841
• 关键词: adduct; benzopyrenes; biological models; biomarker; chemical carcinogen; chemical carcinogenesis; cytotoxicity; environmental stressor; fluorescence microscopy; high performance liquid chromatography; human tissue; laboratory mouse; lung injury; occupational hazard; organ; petroleum oil; pyrenes; radiotracer; skin absorption; toxicant interaction; transmission electron microscopy

Synergy between components of mixtures is a difficult problem for risk assessment, particularly when one or more of the components is not itself active. We have found that when certain mixtures of carcinogens and non-carcinogens are applied topically, the DNA binding of the carcinogens is increased significantly in the lung. Enhancement of dermal absorption and saturation of dermal metabolism are two possible mechanisms where non-carcinogens can cause increased internal organ dose of carcinogens. We will explore the potential for these interactions in acute, sub-chronic and chronic exposures studies with a model carcinogen, benzo(a)pyrene and two non-carcinogens, pyrene and kerosene. The focus of the research will be to determine whether and how non-carcinogens can alter the target organ effects of a model carcinogen and to develop a risk assessment model for mixtures based on the interaction between carcinogenic and non-carcinogenic components in the whole animal. This work is an attempt to deal this potential problem in a systematic way. Since millions of persons in occupations are exposed to carcinogenic complex mixtures, these data should be very useful in decreasing the uncertainties of risk assessment of these exposures.

混合组件之间的协同作用是风险评估的困难问题，尤其是当一个或多个组件本身不活跃时。 我们发现，当局部应用致癌物和非致癌物的某些混合物时，肺癌的DNA结合显着增加。 真皮吸收和真皮代谢的饱和度是两种可能的机制，非冲突剂会导致内器官剂量增加的致癌物。 我们将通过模型致癌，苯并（A）pyrene和两种非连续性元，pyrene和pyrene和煤油探索急性，降低和慢性暴露研究中这些相互作用的潜力。 该研究的重点是确定非洲毒素是否可以改变模型致癌物的靶器官效应，并根据整个动物中致癌和非致癌成分之间的相互作用开发混合物的风险评估模型。 这项工作是试图以系统的方式解决这一潜在问题的尝试。由于数以百万计的职业人员暴露于致癌的复杂混合物中，因此这些数据在减少对这些暴露的风险评估的不确定性方面应该非常有用。