Biomarker Matrix for Genotoxicity Mode of Action
遗传毒性作用模式的生物标志物矩阵
基本信息
- 批准号:8712980
- 负责人:
- 金额:$ 15万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2014
- 资助国家:美国
- 起止时间:2014-08-15 至 2015-01-31
- 项目状态:已结题
- 来源:
- 关键词:ATM activationAddressAnimal ModelAtherosclerosisBiological AssayBiological MarkersCarcinogensCell CycleCell LineCell NucleusCellsChemicalsChromosome abnormalityDNADNA DamageDNA Single Strand BreakDNA-PKcsDataDiseaseExhibitsFlow CytometryFluorescenceGene MutationGeneticGoalsHealthHereditary DiseaseHumanIn VitroIncidenceKineticsLabelLiverLogistic RegressionsMammalian CellMeasuresMediatingMembrane PotentialsModelingModificationMutagenicity TestsPerformancePhasePlagueProcessProtocols documentationRattusReadingReagentRecoveryRegression AnalysisRiskSecondary toSensitivity and SpecificitySolutionsSpecificityStatistical ModelsStructureSystemTestingToxic effectToxicogeneticsTrainingTreatment ProtocolsValidationWorkbasecarcinogenesisclastogencytotoxicitygenotoxicityhigh throughput analysisin vivomethod developmentmicronucleusmitochondrial membranepredictive modelingpreferenceproduct developmentprototypepublic health relevancerepairedresearch studyresponsetool
项目摘要
DESCRIPTION (provided by applicant): It is well recognized that current batteries of genetic toxicology assays exhibit relatively high sensitivity, meaning they effectively identify genotoxic carcinogens. However, a critical deficiency with current approaches exists-namely, the specificity of the in vitro mammalian cell genotoxicity tests is low, as they yield a high incidenc of positive results that do not have in vivo relevance (so-called "misleading" or "irrelevant" positives). This high incidence of irrelevant in vitro positive results leads to extensive and costy additional testing, often with whole animal models, or else abandonment of potentially valuable products. We will address this major problem with current in vitro mammalian cell genetic toxicity assays by developing commercial kits that enable an automated testing strategy that exhibits both high sensitivity and specificity. This system will categorize positive results according to the predominant mode of genotoxic activity, and importantly, will reliably identify irrelevant mode(s) of action that are likely to be nonoperational in vivo. A secondary objective of
the proposed work is the development of methods for characterizing clastogens. That is, we will develop tools that elucidate whether clastogenic activity is the result of DNA-reactivity, or whether it is mediated by an indirect mechanism.
描述(由申请人提供):众所周知,目前的遗传毒理学试验组具有相对较高的灵敏度,这意味着它们可有效识别遗传毒性致癌物。然而,目前的方法存在一个关键的缺陷,即体外哺乳动物细胞遗传毒性试验的特异性较低,因为它们产生的阳性结果的发生率很高,而这些结果与体内无关(所谓的“误导性”或“不相关”阳性)。这种不相关的体外阳性结果的高发生率导致广泛和昂贵的额外测试,通常使用整个动物模型,或者放弃潜在有价值的产品。我们将通过开发商业化试剂盒来解决目前体外哺乳动物细胞遗传毒性检测的这一主要问题,该试剂盒能够实现具有高灵敏度和特异性的自动化检测策略。该系统将根据遗传毒性活性的主要模式对阳性结果进行分类,重要的是,将可靠地识别可能在体内不起作用的不相关作用模式。的次要目的
拟议的工作是制定鉴定断裂物的方法。也就是说,我们将开发工具,阐明是否致染色体断裂活性是DNA反应性的结果,或者它是否是由间接机制介导的。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Jeffrey C Bemis其他文献
Jeffrey C Bemis的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Jeffrey C Bemis', 18)}}的其他基金
Modeling the Responsiveness of Sensitive Populations to Genotoxic Agents Using DNA Repair Inhibitors
使用 DNA 修复抑制剂模拟敏感人群对基因毒性药物的反应性
- 批准号:
10734425 - 财政年份:2023
- 资助金额:
$ 15万 - 项目类别:
High Throughput Screen and High Information Follow-Up Tests for Genotoxicants
基因毒物的高通量筛选和高信息后续测试
- 批准号:
10605311 - 财政年份:2022
- 资助金额:
$ 15万 - 项目类别:
High Throughput Screen and High Information Follow-Up Tests for Genotoxicants
基因毒物的高通量筛选和高信息后续测试
- 批准号:
10576559 - 财政年份:2022
- 资助金额:
$ 15万 - 项目类别:
High Throughput Screen and High Information Follow-Up Tests for Genotoxicants
基因毒物的高通量筛选和高信息后续测试
- 批准号:
10255405 - 财政年份:2021
- 资助金额:
$ 15万 - 项目类别:
Development of rat liver 3D organoid methods to address genotoxicity screening
开发大鼠肝脏 3D 类器官方法来解决遗传毒性筛查
- 批准号:
10075486 - 财政年份:2020
- 资助金额:
$ 15万 - 项目类别:
Next Generation Testing Strategies for Assessment of Genotoxicity
下一代遗传毒性评估测试策略
- 批准号:
9807074 - 财政年份:2018
- 资助金额:
$ 15万 - 项目类别:
Validation of Cross-Species Biomarkers of DNA Damage
DNA 损伤跨物种生物标志物的验证
- 批准号:
9769037 - 财政年份:2018
- 资助金额:
$ 15万 - 项目类别:
Biomarker Matrix for Genotoxicity Mode of Action
遗传毒性作用模式的生物标志物矩阵
- 批准号:
9002963 - 财政年份:2014
- 资助金额:
$ 15万 - 项目类别:
Biomarker Matrix for Genotoxicity Mode of Action
遗传毒性作用模式的生物标志物矩阵
- 批准号:
8914767 - 财政年份:2014
- 资助金额:
$ 15万 - 项目类别:
相似海外基金
Rational design of rapidly translatable, highly antigenic and novel recombinant immunogens to address deficiencies of current snakebite treatments
合理设计可快速翻译、高抗原性和新型重组免疫原,以解决当前蛇咬伤治疗的缺陷
- 批准号:
MR/S03398X/2 - 财政年份:2024
- 资助金额:
$ 15万 - 项目类别:
Fellowship
CAREER: FEAST (Food Ecosystems And circularity for Sustainable Transformation) framework to address Hidden Hunger
职业:FEAST(食品生态系统和可持续转型循环)框架解决隐性饥饿
- 批准号:
2338423 - 财政年份:2024
- 资助金额:
$ 15万 - 项目类别:
Continuing Grant
Re-thinking drug nanocrystals as highly loaded vectors to address key unmet therapeutic challenges
重新思考药物纳米晶体作为高负载载体以解决关键的未满足的治疗挑战
- 批准号:
EP/Y001486/1 - 财政年份:2024
- 资助金额:
$ 15万 - 项目类别:
Research Grant
Metrology to address ion suppression in multimodal mass spectrometry imaging with application in oncology
计量学解决多模态质谱成像中的离子抑制问题及其在肿瘤学中的应用
- 批准号:
MR/X03657X/1 - 财政年份:2024
- 资助金额:
$ 15万 - 项目类别:
Fellowship
CRII: SHF: A Novel Address Translation Architecture for Virtualized Clouds
CRII:SHF:一种用于虚拟化云的新型地址转换架构
- 批准号:
2348066 - 财政年份:2024
- 资助金额:
$ 15万 - 项目类别:
Standard Grant
The Abundance Project: Enhancing Cultural & Green Inclusion in Social Prescribing in Southwest London to Address Ethnic Inequalities in Mental Health
丰富项目:增强文化
- 批准号:
AH/Z505481/1 - 财政年份:2024
- 资助金额:
$ 15万 - 项目类别:
Research Grant
ERAMET - Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
ERAMET - 快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
- 批准号:
10107647 - 财政年份:2024
- 资助金额:
$ 15万 - 项目类别:
EU-Funded
BIORETS: Convergence Research Experiences for Teachers in Synthetic and Systems Biology to Address Challenges in Food, Health, Energy, and Environment
BIORETS:合成和系统生物学教师的融合研究经验,以应对食品、健康、能源和环境方面的挑战
- 批准号:
2341402 - 财政年份:2024
- 资助金额:
$ 15万 - 项目类别:
Standard Grant
Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
- 批准号:
10106221 - 财政年份:2024
- 资助金额:
$ 15万 - 项目类别:
EU-Funded
Recite: Building Research by Communities to Address Inequities through Expression
背诵:社区开展研究,通过表达解决不平等问题
- 批准号:
AH/Z505341/1 - 财政年份:2024
- 资助金额:
$ 15万 - 项目类别:
Research Grant