MECHANISMS OF CHEMICAL LYMPHOMAGENESIS

这项研究计划的目标是全面分析 在RF品系小鼠的皮肤上涂上致癌物质的机制， 3-甲基胆蒽(MCA)，迅速诱导近100%的发病率 胸腺淋巴瘤。该计划中的每个项目都将解决这个问题 从独特的角度来看，使用不同的策略和不同的 技术范围从体内研究到培养的淋巴瘤 利用重组DNA技术对细胞系进行分子研究。单元格 原发淋巴瘤和淋巴瘤细胞系的特征 在抗原学和病毒学上，以及它们诱导 移植免疫和特异性细胞免疫反应将是 下定决心。非孟德尔式的母性传播因子的性质 抑制内源性小鼠白血病病毒表达的RF小鼠 (MuLV)和自发性淋巴瘤将被研究。一位最近发现的 抵抗MCA诱导淋巴瘤的显性基因--和 可能也会导致淋巴瘤--将按顺序进行研究 以确定其地图位置和作用机制。的作用 内源性MuLV在MCA淋巴肿瘤发生中的作用将被广泛研究。单元格 将检查是否存在新的MuLV前病毒信息 通过与来自胚胎细胞或来自 正常淋巴细胞和任何这类新的前病毒将被映射到 细胞基因组。重组DNA技术将用于 含病毒胞质RNA转录本的鉴定 将提供信息以尝试识别宿主基因(候选 细胞癌基因)及其产物 基因组重排。对总体差异的详细检查 将在正常细胞和淋巴瘤细胞之间进行基因表达。广度 MCA诱导的RF淋巴瘤系统中的哪些发现可以作为 推广到这个和其他淋巴瘤诱发的其他系统 将对小鼠品系进行探索。

The goal of this research program is a comprehensive analysis of the mechanisms whereby painting the skin of RF strain mice with the carcinogen, 3-methylcholanthrene (MCA), rapidly induces a near 100 percent incidence of thymic lymphoma. Each project in the program will approach the problem from a unique perspective, using different strategies and different techniques ranging from studies in vivo through work with cultured lymphoma cell lines to molecular studies by recombinant DNA techniques. Cells of primary lymphomas and of lymphoma cell lines will be characterized antigenically and virologically, and their capacity to elicit transplantation immunity and specific cellular immune responses will be determined. The nature of the nonmendelian, maternally transmitted factor of RF mice which suppresses expression of endogenous murine leukemia virus (MuLV) and spontaneous lymphoma will be studied. A recently identified dominant gene which confers resistance to MCA induction of lymphoma--and possibly to x-ray induction of lymphoma, as well--will be studied in order to determine its map location and its mechanism of action. The role of endogenous MuLV in MCA lymphomagenesis will be extensively explored. Cells of RF lymphomas will be examined for new MuLV proviral information present in their chromosomal DNA by comparison with DNA from embryo cells or from normal lymphocytes, and any such new proviruses will be mapped within the cellular genome. Recombinant DNA techniques will be used in the characterization of cytoplasmic RNA transcripts containing viral information will be made in an attempt to identify host genes (candidate cellular oncogenes) and their products that are expressed as a result of genomic rearrangements. A detailed examination of differences in overall gene expression between normal and lymphoma cells will be made. The extent to which findings in the system of MCA-induced RF lymphomas can be generalized to other systems of lymphoma induction in this and other strains of mice will be explored.