Global Responses to Aflatoxin B1 & Alkylating Agents

全球对黄曲霉毒素 B1 的应对措施

• 批准号: 6932102
• 负责人: LEONA D. SAMSON
• 金额: $ 155.18万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-30 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6932102
• 关键词: DNA damage; aflatoxins; alkylating agents; chemical carcinogen; environmental exposure; environmental toxicology

DESCRIPTION (provided by applicant) In response to RFA:ES-01-002, this is an application to become a member of the NIEHS-sponsored Toxicogenomics Research Consortium. The have proposed a highly integrated plan to explore the transcriptional responses of a variety of organisms, including humans, to a broad range of toxic agents found in the environment. Transcriptional profiling is expected to reveal a truly global view of how cells, tissues and animals attempt to recover, not always successfully from environmental insults. The investigators hope to learn what features of environmentally induced transcriptional responses are predictive of success or failure, and in addition to learn what features correlate with specific outcomes of toxic exposures, for instance, cell death, apoptosis, mutagenesis and carcinogenesis. The model environmental agents to be studied are Aflatoxin B1 and its metabolites, plus a range of SNI and SN2 alkylating agents. Together these agents are representative of toxic agents found in the external environment, food supply, the endogenous cellular environment, and the cancer chemotherapy clinic. The model organisms and cell systems whose transcriptional responsiveness will be scrutinized include E. coli, S. cerevisiae, cultured rodent and human cell lines, engineered rat and mouse liver tissues, rats and mice. The investigators have integrated an in vitro tissue engineering Project into this application with the goal of developing an alternative to using animals to test for toxicity and carcinogenicity. It seems to the investigators that appropriate transcriptional responsiveness in this system represents a rigorous test of its similarity to in vivo tissues. Two platforms for mRNA profiling will be employed, namely, Affymetrix GeneChip DNA oligonucleotide microarrays, and cDNA arrays fabricated in the MIT BioMicro Center. The Microarraying and Bioinformatics Core will have its center of gravity in the MIT BioMicro Center, and this Core will serve as the focal point for three Research Projects and the Toxicology Research Core Project (TRCP). The TRCP activities will be closely aligned with the activities of the other 4 or 5 members of the Toxicogenomics Research Consortium. Together the overarching goals will be to establishing good working practices in transcriptional profiling as it relates to the area of toxicogenomics, and to contribute to the development of an extensive relational database as a repository for high quality data emerging from the field of toxicogenomics. The investigators anticipate that this research will uncover a myriad of hitherto unknown ways in which cells respond to environmental agents.

描述（由申请人提供） 为了响应RFA：ES-01-002，这是成为成员的应用程序 NIEHS赞助的毒物学研究联盟。提出了一个 高度集成的计划来探索各种的转录响应 在包括人类在内的生物，到达广泛的有毒剂 环境。记录分析有望揭示真正的全球 观察细胞，组织和动物如何尝试恢复，并非总是 成功地来自环境侮辱。调查人员希望了解什么 环境引起的转录响应的特征是预测的 成功或失败，除了了解哪些功能与 有毒暴露的特定结果，例如细胞死亡，凋亡， 诱变和癌变。 要研究的模型环境药物是黄曲霉毒素B1及其 代谢物，以及一系列SNI和SN2烷基化剂。在一起 代理人是在外部环境中发现的有毒药物的代表， 食物供应，内源性细胞环境和癌症化学疗法 诊所。转录的模型生物和细胞系统 响应能力将被审查包括大肠杆菌，酿酒酵母，培养 啮齿动物和人类细胞系，工程化的大鼠和小鼠肝组织，大鼠和大鼠 老鼠。研究人员已经整合了体外组织工程 将其投入到该应用程序中，目的是开发一种替代方案 使用动物测试毒性和致癌性。看来 调查人员在该系统中适当的转录响应能力 代表其与体内组织相似性的严格测试。 将采用两个用于mRNA分析的平台，即Affymetrix Genechip DNA寡核苷酸微阵列和MIT中制造的cDNA阵列 生物学中心。微阵列和生物信息学核心将具有 麻省理工学院BioMicro中心的重心，该核心将作为 三个研究项目和毒理学研究核心的焦点 项目（TRCP）。 TRCP活动将与 其他4或5个毒物学研究成员的活动 财团。共同的总体目标是建立良好 转录分析的工作实践与该区域有关 毒理学学，并为广泛的发展做出贡献 关系数据库作为从 毒理学领域。调查人员预计这项研究将 揭示了迄今为止无数细胞反应的未知方式 环境代理。