MOLECULAR EVALUATION OF 2,2-BIS(BROMOMETHYL)-1,3-PROPANEDIOL(BMP) B6C3F1 MOUSE

2,2-双(溴甲基)-1,3-丙二醇(BMP) B6C3F1 小鼠的分子评价

• 批准号: 6289917
• 负责人: Robert C Sills
• 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/6289917
• 关键词: animal genetic material tag; carcinogen testing; chemical carcinogen; chemical carcinogenesis; laboratory mouse; loss of heterozygosity; lung neoplasms; mutagen testing; mutagens; ozone; point mutation; protooncogene

Summary of Work: The only K-ras mutation detected was at codon 12 (GGT to GAT), and was identified in half of the neoplasms from exposure concentrations of 312, 625 and 1,250 ppm BMP and in feed controls. Our study suggests that mutations in the K-ras gene are involved in B6C3F1 lung carcinogenesis following BMP exposure. Based on the detection of the K-ras mutation, and the recent identification of a major lung susceptibility locus mapped to the distal part of chromosome 6 in the region of the K-ras gene, we are examining the lung tumors for loss of heterozygosity (LOH) on distal chromosome 6. To date allelic imbalances on chromosome 6 have been detected in BPM induced mouse lung neoplasms. These studies have been extended to include evaluation of ozone induced neoplasms. Also being evaluated are BMP induced Harderian gland neoplasms. - Neither Human Subjects nor Human Tissues

工作总结：唯一检测到的K-ras突变位于第12密码子(GGT到GAT)，并在一半的肿瘤中发现，从312、625和1250ppm的BMP暴露浓度和饲料对照中发现。我们的研究表明，K-ras基因突变与BMP暴露后B6C3F1肺癌的发生有关。基于K-ras突变的检测，以及最近定位于6号染色体远端K-ras基因区域的一个主要肺易感基因座，我们正在检测6号染色体远端杂合性缺失(LOH)。迄今为止，在BPM诱发的小鼠肺肿瘤中发现了6号染色体上的等位基因失衡。这些研究已经扩展到包括对臭氧引起的肿瘤的评估。骨形态发生蛋白引起的哈德氏腺肿瘤也在评估中。-既不是人体受试者，也不是人体组织