体细胞融合在糖皮质激素作用研究中的应用

U Gehring, E B Thompson
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摘要

本文简要描述了细胞融合和杂交细胞形成的基本现象,并讨论了体细胞杂交在分化细胞功能表达研究中的潜力。细胞杂交技术已被应用于两类细胞对糖皮质激素的反应。在可诱导细胞与不可诱导细胞的杂交体中研究了特定蛋白质的诱导。大多数研究涉及肝脏特异性酶酪氨酸氨基转移酶,其诱导性在大多数肝癌细胞与非肝癌细胞的杂交中消失。然而,染色体分离后,部分杂交细胞的诱导性又重新出现。本文讨论了目前有关细胞控制诱导性的观点。细胞杂交研究中调查的另一个主要的糖皮质激素反应系统是淋巴细胞,它们在暴露于类固醇时会被杀死。这种敏感细胞与几种抗糖皮质激素的淋巴细胞系杂交,发现敏感性优于抗性。然而,与野生型亲本细胞相比,敏感淋巴细胞与抗性淋巴细胞杂交后产生抗性的频率增加了。在具有糖皮质激素特异性受体系统缺陷的不同类型抗性细胞之间的杂交中,没有发现对类固醇敏感性的互补。
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Somatic cell fusion in the study of glucocorticoid action.

The basic phenomena of cell fusion and hybrid cell formation are briefly described and the potential of somatic cell hybridization in studies on the expression of differentiated cellular functions is discussed. The technique of cell hybridization has been applied to two types of cellular responses to glucocorticoids. The induction of specific proteins has been investigated in hybrids of inducible cells with uninducible cells. Most studies dealt with the liver-specific enzyme tyrosine aminotransferase, whose inducibility was extinguished in the majority of the hybrids between hepatoma and nonliver cells. However, upon chromosome segregation, inducibility reappeared in some of these hybrid cells. The current ideas about cellular control of inducibility are discussed. The other major glucocorticoid-responsive system investigated in cell hybridization studies consists of lymphoid cells which are killed when exposed to the steroid. Such sensitive cells were hybridized with several types of glucocorticoid-resistant lymphoid lines, and sensitivity was found to be dominant over resistence. Hybrids between sensitive and resistant lymphoid cells, however, showed an increase in the frequency at which resistance occurred as compared to the rate observed with the wild-type parental cells. No complementation to steroid sensitivity was found in hybrids between different types of resistant cells with defects in the glucocorticoid-specific receptor system.

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