PRECLINICAL EVALUATIONS OF INTERMEDIATE ENDPOINTS

中间终点的临床前评估

• 批准号: 2302689
• 负责人: G CLINTON
• 金额: $ 58.06万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-09-30 至 1997-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2302689
• 关键词: PRECLINICAL; EVALUATIONS; INTERMEDIATE; ENDPOINTS

The objective of this project is to determine the mechanism of action of 4HPR, retinyl acetate and 9 cis retinoic acid. N-methyl-N-nitrosourea (MNU) is being used to generate mammary tumors in Sprague-Dawley rats. The animals are being exposed to the three retinoids (9-cis retinoic acid, 4 HPR, and retinyl acetate) for six weeks. Individual livers, mammary glands, and lungs are examined for the expression of the RNAs coding for RAR alpha, RAR beta , RXR alpha and one other gene which is modulated by retinoids. Mammary tumors from rats treated with MNU-alone or rats treated with MNU plus retinoid are used to determine the long term effects of the retinoids on tumor tissues. The levels of apoptosis in these tissues are being measured employing standard published techniques for measuring apoptosis. The genetic changes associated with mammary tumorigenesis in rodents and humans are being examined. Liver samples are also being studied to determine whether potential markers on the rat genome display heterozygosity at the specific sites to be examined. Mammary tumors and a more limited number of "normal" regions of breast tissue are being examined for loss of heterozygosity in regions syntenic to the human 7Q region in these animal tumors. DMBA -induced tumors from Fl mice are also being examined for the loss of the region syntenic to the human 7Q region.

本项目的目的是确定 4 HPR、乙酸视黄酯和9顺式视黄酸。N-甲基-N-亚硝基脲 (MNU)被用于在Sprague-Dawley大鼠中产生乳腺肿瘤。的 动物暴露于三种类视色素（9-顺式视黄酸，4 HPR和乙酸视黄酯）持续6周。 单个肝脏，乳腺 检查腺体和肺中编码以下蛋白的RNA的表达： RAR α、RAR β、RXR α和另一种基因，其由 类维生素A。MNU单独给药大鼠或给药大鼠的乳腺肿瘤 与MNU加类维生素A一起使用，用于确定 肿瘤组织中的类维生素A。这些组织中的细胞凋亡水平是 采用标准公布的测量技术进行测量 凋亡乳腺癌发生的遗传学改变 啮齿动物和人类正在接受检查。肝脏样本也在 研究以确定大鼠基因组上的潜在标记是否显示 在特定位点的杂合性进行检查。乳腺肿瘤和 更有限数量的乳房组织的“正常”区域正在被 检查与人7 Q同线区域的杂合性缺失 在这些动物肿瘤中。来自F1小鼠的DMBA诱导的肿瘤也是 正在检查与人类7 Q区域同线的区域的丢失。