IDENTIFICATION AND ISOLATION OF C-FMS PROTOONCOGEN FROM F344/N RAT LEUKEMIA

F344/N 大鼠白血病 C-FMS 原癌原的鉴定和分离

• 批准号: 3876855
• 负责人: J E FRENCH
• 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/3876855
• 关键词: aging; alveolar macrophages; cell differentiation; chemical carcinogenesis; chromosome deletion; chromosome translocation; colony stimulating factor; cytokine receptors; disease /disorder model; environment related neoplasm /cancer; gene expression; genetic mapping; growth factor receptors; hematopoietic growth factor; karyotype; laboratory rat; leukemia; macrophage; molecular genetics; neoplasm /cancer diagnosis; neoplasm /cancer genetics; neoplasm /cancer transplantation; neoplastic cell; nucleic acid hybridization; nucleic acid probes; oncogenes; protooncogene; surface antigens; tumor antigens

Understanding the chemically induced or associated occurrence of mononuclear cell leukemia (MNCL) in NTP two-year chronic toxicology and carcinogenesis studies may be complicated by the high background rate of this tumor in aging F344 rats (20 to 30% after 24 months of age). A F344 rat leukemia transplant model has been developed to characterize the biology of this rodent leukemia and to investigate the relationship between age-related, environmental factors, and/or chemically related or modulated (promoted) leukemia. As described previously, karyotype analysis indicates that both spontaneous and serially transplanted leukemia cells have a normal complement of chromosomes (2N=42) with a variant x-subterminal chromosome, but no further details are available on non-random chromosomal changes. Sister chromatid exchange rates in bone marrow cells of aging Fischer 344 rats are about 1.5 times greater than Wistar rats and the background tumor incidence is similarly increased. Studies are in progress to define non-random chromosomal changes (additions, deletions, translocations, etc.) and using high-resolution G-banding techniques and the relationship to the expression of the c-fms protooncogene product (for hematopoietic growth factor receptor, CSF-1). Final results on the identification of c-fms indicate that these rat leukemia cells from both spontaneous (717, untreated, >22 months of age) and transplanted (8/8) leukemias express the fms/CSF-1 receptor as 3.8 kb RNA transcript identical to that expressed by normal rat macrophages. This information is important to the diagnosis and understanding of chemical effects in this rodent model as a surrogate for human exposure to toxic and/or carcinogenic chemicals.

理解化学诱导或相关的发生 单核细胞白血病(MNCL)在NTP两年慢性毒理学和临床试验中的应用 癌症发生的研究可能会因为高本底比率而变得复杂 这种肿瘤发生在老龄F344大鼠(24个月龄后20%至30%)。一架F344 已经建立了大鼠白血病移植模型来表征 探讨这种啮齿动物白血病与生物学的关系 与年龄有关的、环境因素，和/或与化学有关的或调制的 (升级)白血病。如前所述，核型分析表明 自发性和连续移植的白血病细胞都有 染色体的正常组合(2N=42)，具有变异的x-亚末端 染色体，但没有关于非随机染色体的进一步细节 改变。衰老骨髓细胞的姐妹染色单体互换率 Fischer 344大鼠大约是Wistar大鼠的1.5倍，而 背景肿瘤发病率也同样增加。研究正在进行中 为了定义非随机的染色体变化(增加、删除、 易位等)并使用高分辨率G显带技术和 与c-fms原癌基因产物表达的关系 造血生长因子受体，CSF-1)。最终结果： C-FMS鉴定表明，这些大鼠白血病细胞来自于 自发性(717，未经治疗；22个月大)和移植(8/8) 白血病表达FMS/CSF-1受体的3.8kb RNA转录本相同 与正常大鼠巨噬细胞表达的基因相比。这一信息很重要 对这一啮齿动物模型中化学效应的诊断和理解 作为人类暴露在有毒和/或致癌化学物质中的替代品。