CONTROL OF PIGMENT PRODUCTION IN MOUSE MELANOMA CELLS IN VITRO
CONTROL OF PIGMENT PRODUCTION IN MOUSE MELANOMA CELLS IN VITRO
复制标题
体外控制小鼠黑色素瘤细胞色素的产生
作者：
S. Silagi
克隆衍生的无色素黑色素瘤细胞系在DNA合成抑制剂I-β- d -阿拉伯糖醛酸胞嘧啶（ara-C）的亚致死水平下多次被迫产生色素。一个ara- c衍生的黑色素系已被克隆，并在正常培养基上持续产生色素2年。当在细胞周期的S期连续4天以1.8 x 10-5 M的脉冲给药于同步细胞时，抑制剂是最有效的。在实验条件下，亚致死浓度的秋碱和琼脂固化培养基上的生长也诱发了这条线的色素生成，但大量其他生物合成过程的抑制剂没有。黑系是酪氨酸酶（多巴氧化酶）的活跃生产者，而无色素系产生酪氨酸酶活性抑制剂。酶和抑制剂在4°C和-20°C时都不稳定，并且抑制剂在无色素细胞匀浆中的衰变表明残留的DOPA氧化酶活性较低。克隆的黑素色系群体翻倍时间平均为23小时，克隆的无素色系群体翻倍时间平均为16.5小时。在其他黑色素系中也发现了类似的生长速度下降，这被认为是维持这种分化功能的重要因素。快速生长可能与无色素细胞产生一种抑制剂有关。
A clonally derived amelanotic melanoma cell line repeatedly has been forced to produce pigment by the inhibitor of DNA synthesis, I-β-D-arabinofuranosylcytosine (ara-C) at sublethal levels. One ara-C-derived melanotic line has been cloned, and has continued to produce pigment for 2 years on normal medium. The inhibitor is most effective when administered to synchronized cells in four pulses on successive days at 1.8 x 10-5 M during the S phase of the cell cycle. Colcemid at a sublethal concentration, and growth on medium solidified with agar also evoked pigment production in this line, but a large number of other inhibitors of biosynthetic processes did not, under the conditions tested. The melanotic lines are active producers of tyrosinase (DOPA oxidase), whereas the amelanotic line produces an inhibitor of tyrosinase activity. Both enzyme and inhibitor are labile at 4° C and -20° C, and decay of the inhibitor in homogenates of amelanotic cells reveals a low level of residual DOPA oxidase activity. The mean population doubling time of a cloned melanotic line is 23 hr, and that of a cloned amelanotic line 16.5 hr. A similar decrease in rate of growth is found in other melanotic lines and is believed to be a significant factor in maintaining this differentiated function. Rapid growth may be related to the production of an inhibitor by the amelanotic cells.