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: 6106608
• 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/6106608
• 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 chromosoem 6 have been detected in BPM induced lung neoplasms. These studies have been extended to include evaluation of ozone induced neoplasms. Also being evaluated are BMP induced Harderian gland neoplasms.

工作总结：唯一的K-ras突变 检测到的是第12密码子(GGT到GAT)，并被鉴定为一半 312,625和312,625和 1,250 ppm BMP和饲料控制中。我们的研究表明 K-ras基因突变与B6C3F1肺相关 BMP暴露后的致癌作用。根据检测到的 K-ras突变和最近发现的大肺 易感基因定位于6号染色体远端 K-ras基因的区域，我们正在检查肺肿瘤 6号染色体远端杂合性缺失(LOH) 在BPM中检测到6号染色体上的等位基因不平衡 诱发的肺部肿瘤。这些研究已经扩展到 包括对臭氧引起的肿瘤的评估。也是 评估的是骨形态发生蛋白诱导的哈德氏腺肿瘤。