Fleischmann C M, Fleischmann W R
Department of Microbiology, University of Texas Medical Branch, Galveston.
J Biol Regul Homeost Agents. 1988 Oct-Dec;2(4):173-85.
Interferons have been recognized to have potent in vitro antiproliferative activities in mouse and human systems. To further investigate the kinetics of development of interferons' antiproliferative activities, mouse B-16 melanoma cells were treated with MuIFN-alpha, MuIFN-beta or MuIFN-gamma for various initial periods of time during an 8 day cloning assay. With MuIFN-alpha and MuIFN-beta treatments, maximal expression of antiproliferative activity was attained with 2 to 4 days of interferon treatment. In contrast, with MuIFN-gamma treatment, expression of antiproliferative activity increased with progressively longer periods of time of MuIFN-gamma treatment. These results suggested that B-16 melanoma cells were initially sensitive to all three of the interferons but rapidly became resistant to MuIFN-alpha and MuIFN-beta after 2 to 4 days of treatment. This suggestion was confirmed by cell growth kinetics experiments. The cells which were resistant to the antiproliferative activity of the MuIFN-alpha remained sensitive to the antiviral activity of MuIFN-alpha, suggesting that MuIFN-alpha and MuIFN-beta regulate their antiviral and antiproliferative responses via different mechanisms. The cells which were resistant to the antiproliferative activities of MuIFN-alpha and MuIFN-beta remained sensitive to MuIFN-gamma, suggesting that they were not generally resistant to antiproliferative effects. The cells which were resistant to the antiproliferative activities of the interferons gradually lost their resistance with a half-life of 11 days when they were cultured in the absence of interferons. The differential antiproliferative actions of alpha, beta and gamma interferons observed with murine B-16 melanoma were confirmed in the human system with G-361 melanoma cells.(ABSTRACT TRUNCATED AT 250 WORDS)
干扰素已被公认在小鼠和人类系统中具有强大的体外抗增殖活性。为了进一步研究干扰素抗增殖活性的发展动力学，在为期8天的克隆试验中，在不同的初始时间段用鼠干扰素-α（MuIFN-α）、鼠干扰素-β（MuIFN-β）或鼠干扰素-γ（MuIFN-γ）处理小鼠B-16黑色素瘤细胞。用MuIFN-α和MuIFN-β处理时，干扰素处理2至4天可达到抗增殖活性的最大表达。相比之下，用MuIFN-γ处理时，抗增殖活性的表达随着MuIFN-γ处理时间的延长而增加。这些结果表明，B-16黑色素瘤细胞最初对所有三种干扰素都敏感，但在处理2至4天后迅速对MuIFN-α和MuIFN-β产生抗性。这一推测通过细胞生长动力学实验得到证实。对MuIFN-α抗增殖活性具有抗性的细胞对MuIFN-α的抗病毒活性仍敏感，这表明MuIFN-α和MuIFN-β通过不同机制调节其抗病毒和抗增殖反应。对MuIFN-α和MuIFN-β抗增殖活性具有抗性的细胞对MuIFN-γ仍敏感，这表明它们并非普遍对抗增殖作用具有抗性。对干扰素抗增殖活性具有抗性的细胞在无干扰素培养时，其抗性逐渐丧失，半衰期为11天。在人类G-361黑色素瘤细胞系统中证实了在小鼠B-16黑色素瘤中观察到的α、β和γ干扰素的不同抗增殖作用。（摘要截短于250字）
