MECHANISMS OF CHEMICAL LYMPHOMAGENESIS

这项研究计划的目标是全面分析 用致癌物质涂抹RF品系小鼠的皮肤的机制， 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 从一个独特的角度，使用不同的策略和不同的 从体内研究到培养淋巴瘤 通过重组DNA技术对细胞系进行分子研究。 细胞 原发性淋巴瘤和淋巴瘤细胞系的特征在于 抗原性和病毒学，以及它们引发 移植免疫和特异性细胞免疫应答将是 测定 非孟德尔遗传的母系遗传因素的性质 抑制内源性鼠白血病病毒表达的RF小鼠 （MuLV）和自发性淋巴瘤进行研究。 新近发现的一 显性基因，赋予抵抗MCA诱导淋巴瘤-和 也可能是淋巴瘤的X射线诱导--将被研究， 以确定其地图位置和作用机制。 的作用 将广泛探索MCA淋巴瘤发生中的内源性MuLV。 细胞 的RF淋巴瘤将检查是否存在新的MuLV前病毒信息 通过与来自胚胎细胞的DNA或来自 正常的淋巴细胞，任何这样的新的前病毒将被定位在正常的淋巴细胞内。 细胞基因组 重组DNA技术将用于 含有病毒的细胞质RNA转录物的表征 信息将被用于试图鉴定宿主基因（候选基因 细胞癌基因）及其产物，作为 基因组重排 对总体差异的详细审查 进行正常细胞和淋巴瘤细胞之间的基因表达。 程度 MCA诱导的RF淋巴瘤系统中的发现可能与 推广到其他系统的淋巴瘤诱导在这个和其他 将探索小鼠品系。

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.