ACTIVATION OF ENVIRONMENTAL CHEMICALS BY HEPATOCYTES

肝细胞对环境化学物质的激活

• 批准号: 3965223
• 负责人: J A GOLDSTEIN
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3965223
• 关键词: DNA; antibody; chemical binding; chemical carcinogen; chemical structure function; cytochrome P450; environmental toxicology; human tissue; liver cells; liver metabolism; mutagens; tissue /cell culture; toxicant interaction; toxicant screening; toxin metabolism

The objectives of this study are to examine the activation of precarcinogens to reactive DNA binding and mutagenic metabolites in hepatocytes and S9. 1. The hepatocarcinogen, 2,4-diaminotoluene(DAT), was activated to reactive metabolites which bound to DNA to a greater extent than the nonhepatocarcinogen, 2,6-DAT. The ability of activation to mutagens and DNA binding species was examined. Inhibitors of metabolism were also examined. 2. The ability of constitutive isozymes of P-450 to activate a variety of mutagens was compared. 3. We also evaluated a human cell line, Hep G2, using antibodies to several human P-450s to determine whether the cell line resembled normal human liver cells in its metabolic capability. The goal of this project is to investigate the ability of various liver pathways to activate precarcinogens and to reactive DNA-binding and mutagenic species. The enzymatic composition of a human cell line was compared with that of normal liver to determine whether this human cell line could be expected to metabolize foreign chemicals in a manner similar to normal human liver.

本研究的目的是检查激活 前致癌物对反应性DNA结合和致突变代谢物的影响 肝细胞和S9。 1.肝癌原2，4-二氨基甲苯（DAT）被激活， 与DNA结合的代谢物比 非肝癌原，2，6-DAT。激活诱变剂的能力， 检查DNA结合物质。 代谢抑制剂也是 考察 2. P-450组成型同工酶激活多种细胞因子的能力， 诱变剂进行了比较。 3.我们还评估了人类细胞系Hep G2，使用几种抗体， 人P-450，以确定细胞系是否与正常人相似 肝细胞的代谢能力。 本项目的目的是研究各种肝脏的能力， 激活前致癌物和反应性DNA结合的途径， 致突变物种。 人细胞系的酶组成是 与正常肝脏进行比较，以确定这种人类细胞是否 线可以预期代谢外来化学品的方式类似 正常人的肝脏