DEVELOPMENT OF IN VITRO PROPAGATED F344/N MONONUCLEAR CELL LINK

体外增殖的 F344/N 单核细胞链接的开发

• 批准号: 3918637
• 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/3918637
• 关键词: cell bank /registry; chemical carcinogenesis; gene expression; leukemia; model design /development; monoclonal antibody; neoplasm /cancer classification /staging; neoplasm /cancer diagnosis; neoplasm /cancer genetics; neoplasm /cancer transplantation; neoplastic cell; receptor; surface antigens

The high background incidence of mononuclear cell leukemia (MNCL) in Fischer 344 rats (20 to 30%) confounds the evaluation and interpretation of possible chemical treatment related incidence of MNCL in two-year chronic and carcinogenesis studies. A F344 rat leukemia transplant model has been developed to characterize the biology of this rodent leukemia and to study the tumor biology and determine how chemical treatment effects disease expression. The development and use of in vitro propagated F344/N mononuclear leukemic cells will enhance: (1) development of monoclonal antibodies unique to MNCL for diagnostic purposes and staging of the disease, (2) the use of currently available rat cell surface antigen and receptor data to known cytochemical, morphological and cell biochemistry data and the determination of leukemic cell origin and functional lineage, and (3) the use of in vitro tests to determine the toxicity and carcinogenicity of chemicals under study in the in vivo MNCL transplant model. To date several hybriloma cell lines have been developed that have been determined to secrete antibodies that may be unique to these leukemic cells. Cell separations have been developed that allow separation of different leukemia cell types. These different subsets of leukemia cells have been propagated in vivo through several passages and have been cryopreserved for future characterization, (including monoclonal antibody analysis), and in vitro culture as the methods for diffusion chamber, soft agar, and Dexter type cultures and culture conditions are refined.

单核细胞白血病（MNCL）的高背景发病率 Fischer 344只大鼠（20 - 30%）混淆了评价， 解释可能与化学治疗相关的 2年慢性和致癌研究中的MNCL。 一只F344大鼠 已经开发了白血病移植模型来表征 这种啮齿动物白血病的生物学，研究肿瘤生物学， 确定化学治疗如何影响疾病表达。 的 体外培养F344/N单核细胞的开发和应用 白血病细胞将促进：（1）单克隆抗体的发展 MNCL的特异性抗体，用于诊断目的和分期 疾病，（2）使用目前可用的大鼠细胞表面 抗原和受体数据与已知的细胞化学、形态学和 细胞生化数据和白血病细胞的测定 起源和功能谱系，以及（3）体外试验的使用 确定化学品的毒性和致癌性， 在体内MNCL移植模型中的研究。 迄今为止，已经开发了几种杂交瘤细胞系， 已确定分泌抗体，可能是这些独特的 白血病细胞。 细胞分离技术的发展使得 分离不同类型的白血病细胞。 这些不同 白血病细胞的亚群已经在体内繁殖， 几代人，并已冷冻保存，以备将来使用 表征（包括单克隆抗体分析），以及 体外培养方法为扩散室法、软琼脂法， 改进了Dexter型培养物和培养条件。