Quantitative Genotoxicity Analysis

定量遗传毒性分析

• 批准号: 6651293
• 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: 2002
• 资助国家: 美国
• 起止时间: 2002-09-15 至 2003-09-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6651293
• 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（由申请人提供）：某些环氧乙烷化合物具有致突变性， 致癌，导致不可逆的遗传毒性效应。正因为如此， 环氧乙烷基牙科复合树脂必须是遗传安全的。的目标 该提案旨在鉴定适合使用的非遗传毒性反应性单体 环氧乙烷复合树脂配方中。该项目的具体目标是： 1)以确定拟定制剂中疑似遗传毒性官能团的稳定性 在生理学相关挑战下的单体; 2）评估反应性 单体和同源系列相关化学品的机制为基础的遗传 毒性试验，以识别遗传毒性和非遗传毒性结构， 结构组分; 3）为QSAR（定量）提供遗传毒性数据 结构活动关系），以便具体和可量化 可以确定分子结构与遗传毒性之间的关系; 4)为单体结构项目提供建议 预测为无遗传毒性; 5）评价 作为QSAR预测结果开发的新单体， 验证预测并提供基因安全的单体用于制备 复合树脂QSAR。分析将与分子协调 建模和合理的生物材料设计R 01。新的QSAR预测 将在集成基质树脂/粘合剂系统中开发单体 R01。计划评价50种环氧乙烷化合物。这包括三 科学选择的系列单体和标准化学品。三 系列，芳族，脂族和吡喃环氧乙烷单体，代表那些 对项目的兴趣。在所有系列中，吸电子和 提供电子的取代基和分离这些的分子 效果进行了评估。因此，该项目提供了一个系统的过程， 调整含环氧乙烷化合物的结构，使其对基因安全 牙科单体的高反应性树脂组分的兴趣， 程序项目。