CONTROL MECHANISMS OF DIFFERENTIATION AND MALIGNANCY

我们的研究主要是为了阐明 调节基因作用的化合物在鼠病毒诱导的 红白血病细胞及其衍生的细胞系。 我们继续 研究生物反应调节剂的作用机制，因为 尚不清楚DMSO或各种不相关的化合物如何起作用， 触发红细胞分化程序。 萘丁酸酯对病毒诱导的小鼠红白血病细胞作用的研究 揭示了它们并没有经历通常 伴随着分化的诱导。 治疗4天后， DMSO或HMBA，两种有效的诱导剂，大多数细胞都致力于 红细胞途径，并进行终末分化，在缺乏 诱导物，而用萘丁酸酯处理的细胞在细胞内“去分化”， 从培养基中除去诱导物后48小时。 14 C-萘丁酸摄取 研究表明，它可能通过不同于DMSO的机制发挥作用 还有HMBA 蛋白质（组蛋白除外）的模式与亲和力， 未分化和分化红白血病细胞的ss或ds DNA 也在进行比较。 用DMSO诱导后， 出现，而另一种DNA结合蛋白消失。 的研究 其他诱导剂的作用和特异性DNA的结合正在进行中。 在我们的FLvac 用牛痘病毒双重感染的细胞， 对诱导的反应，逆转录病毒整合的模式和 gp 70、gp 52和gp 30的表达似乎没有改变。 痘苗 在合成病毒的细胞核中发现的DNA序列， 整合 我们持续开发人类造血细胞系 感染牛痘的人正在使用它们来研究诱导的效果。 分化 （百万）

Our studies are directed primarily toward elucidating the mechanism of action of compounds which modulate gene action in murine virus-induced erythroleukemia cells and the lines derived from them. We continue to investigate the mechanism of action of biological response modifiers, since it is not understood how DMSO or a variety of unrelated compounds act to trigger the program of erythroid differentiation. Studies on Nabutyrate-treated murine virus-induced erythroleukemia cells revealed that they do not undergo the morphological alteration that usually accompanies induction of differentiation. After 4 days of treatment with DMSO or HMBA, two potent inducers, most of the cells are committed to the erythroid pathway and proceed to terminal differentiation in the absence of the inducer whereas cells treated with Nabutyrate "dedifferentiate" within 48 hrs after the inducer is removed from the medium. 14C-Nabutyrate uptake studies suggest it may act through mechanisms different from those of DMSO and HMBA. The patterns of proteins (other than histones) with affinity for ss or ds DNA in undifferentiated and differentiated erythroleukemia cells are also being compared. After induction with DMSO, a new nuclear protein appears whereas another DNA-binding protein disappears. Studies on the effect of other inducers and the binding of specific DNAs are underway. In our FLvac cells, which are dually infected with vaccinia virus, the response to induction, the pattern of retroviral integration and the expression of gp70, gp52, and gp30 do not appear to be altered. Vaccinia DNA sequences, found in the nucleus of cells synthesizing virus, are not integrated. We have developed human hematopoietic cell lines persistently infected with vaccinia are using them to study the effect of induced differentiation. (M)