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: 6432259
• 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/6432259
• 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. Publication is expected in 2001.

工作总结：检测到的唯一 K-ras 突变位于密码子 12（GGT 到 GAT），并且在暴露浓度为 312、625 和 1,250 ppm BMP 的肿瘤中以及饲料对照中发现了一半的突变。 我们的研究表明，K-ras 基因的突变与 BMP 暴露后 B6C3F1 肺癌的发生有关。 基于 K-ras 突变的检测，以及最近对映射到 K-ras 基因区域中 6 号染色体远端部分的主要肺部易感位点的鉴定，我们正在检查肺部肿瘤中 6 号远端染色体上的杂合性丢失 (LOH)。迄今为止，在 BPM 诱导的小鼠肺肿瘤中已检测到 6 号染色体上的等位基因不平衡。 这些研究已扩展到包括臭氧诱发肿瘤的评估。 还在评估的是 BMP 诱导的哈德氏腺肿瘤。预计于 2001 年出版。