Quantitative Genotoxicity Analysis

定量遗传毒性分析

• 批准号: 6522186
• 负责人: DAVID M YOURTEE
• 金额: $ 11.89万
• 依托单位: UNIVERSITY OF MISSOURI KANSAS CITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-15 至 2006-09-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6522186
• 关键词: DNA damage; biomaterial compatibility; biomaterial evaluation; cell line; chemical structure function; composite resins; ethylene oxide; mutagen testing; toxicant screening

DESCRIPTION (provided by applicant): Some oxirane compounds are mutagenic and carcinogenic causing irreversible genotoxic effects. Because of this, oxirane-based dental composite resins must be genetically safe. The goal of this proposal is to identify non-genotoxic reactive monomers suitable for use in oxirane composite resin formulations. The specific aims in this project are: 1) to determine stability of suspected genotoxic functional groups in proposed monomers under physiologically relevant challenges; 2) to evaluate the reactive monomers and homologous series of related chemicals by mechanism based genetic toxicity testing to identify genotoxic and non-genotoxic structures and structure components; 3) to provide genotoxicity data for QSAR (Quantitative Structure Activity Relationships) so that specific and quantifiable relationships between molecular structure and genotoxicity can be identified; 4) to provide recommendations to the program project on structures of monomers that are predicted to be non-genotoxic and; 5) to evaluate the genotoxicity of new monomers developed as a consequence of QSAR predictions for purpose of validating predictions and providing gene-safe monomers for preparation of composite resins. QSAR. Analysis will be in coordination with the Molecular Modeling and Rational Biomaterials Design R01. QSAR predictions for new monomers will be developed in the Integrated Matrix Resin/Adhesives Systems R01. It is planned to evaluate 50 oxirane compounds. This includes three scientifically selected series of monomers and reference chemicals. The three series, aromatic, aliphatic and pyran oxirane monomers, represent those of interest to the program project. In all series, electron withdrawing and electron donating substituents are represented and molecules tat isolate these effects are evaluated. Thus, this project provides a systematic process to tailor the structure of oxirane containing compounds and make them gene-safe dental monomers for the highly reactive resin components of interest to this program project.

描述(申请人提供)：一些环氧乙烷化合物具有致突变性和 致癌物质造成不可逆的遗传毒性效应。正因为如此， 以环氧乙烷为基础的牙科复合树脂必须是遗传安全的。的目标是 这项建议是为了确定适合使用的非遗传毒性反应性单体。 在环氧乙烷复合树脂配方中。这个项目的具体目标是： 1)确定提出的可疑遗传毒性官能团的稳定性 生理相关挑战下的单体；2)评估反应性 基于机理遗传的单体及相关化学物质系列 毒性测试，以确定遗传毒性和非遗传毒性结构和 结构组分；3)提供定量构效关系的遗传毒性数据 构建活动关系)，以便具体和可量化 可以确定分子结构和遗传毒性之间的关系； 4)为项目项目提供单体结构方面的建议 被预测为非遗传毒性的；5)评估 作为QSAR预测的结果而开发的新单体 验证预测并为其制备提供基因安全单体 复合树脂。定量构效关系。分析将与分子科学相协调 建模和合理的生物材料设计R01。新化合物的QSAR预测 单体将在集成的基质树脂/胶粘剂系统中开发 R01。计划对50种环氧乙烷化合物进行评估。这包括三个 经过科学选择的系列单体和参考化学品。三位一体 系列，芳香族，脂肪族和吡喃环氧烷单体，代表 对计划项目感兴趣。在所有系列中，电子撤回和 给电子取代基是代表的，分子tat分离了它们 对影响进行评估。因此，这个项目提供了一个系统的过程来 调整含有环氧乙烷的化合物的结构，使其具有基因安全性 用于高活性树脂组分的牙科单体 计划项目。