RABINOVITCH M, BRENTANI R, FERREIRA S, FAUSTO N, MAACK T
J Biophys Biochem Cytol. 1961 May;10(1):105-12. doi: 10.1083/jcb.10.1.105.
Acid azo dyes, most of them naphtholdisulfonic acid derivatives, were given intraperitoneally to rats and their effect on "alkaline" ribonuclease activity was studied in total homogenates of kidney cortex and liver. Acid treatment was used to release bound enzyme activity. Several of the dyes, including trypan blue, increased RNase activity in both organs 3 days after administration of single doses, while others, like Evans blue, were inactive. Activity was apparently bound to the sulfonic substitution in the 3, 6 positions in the naphthalene rings, substitutions in the benzidine rings being not critical. All of the active and most of the inactive compounds were taken up by tubule cells of kidney cortex and by reticular and parenchymal cells of liver. While the effect on both liver and kidney was obtained 1 day after trypan blue administration, RNase remained increased for only about 3 days in the first organ, and for at least a month in the second. However, repeated trypan blue doses increased liver enzyme activity for at least 9 days. Serum RNase activity was decreased after trypan blue administration. Ethionine administration together with trypan blue markedly blocked the effect of the dye on liver RNase activity; simultaneously given methionine partially reversed the action of the antimetabolite. This suggests that de novo synthesis of RNase is induced in liver by trypan blue. The action of ethionine on the kidney RNase response to trypan blue was less marked although significant; in view of the possible kidney uptake of the plasma enzyme, interpretation of this finding must be postponed. Results are discussed with reference to the mechanism of the structural specificity of the compounds used, cytological localization of the dyes and their mechanism of action on liver and kidney RNase.
酸性偶氮染料，其中大多数是萘二磺酸衍生物，经腹腔注射给予大鼠，并在肾皮质和肝脏的全匀浆中研究它们对“碱性”核糖核酸酶活性的影响。采用酸处理来释放结合的酶活性。几种染料，包括锥虫蓝，在单次给药3天后可增加两个器官中的核糖核酸酶活性，而其他染料，如伊文思蓝，则无活性。活性显然与萘环3、6位上的磺酸取代有关，联苯胺环上的取代并不关键。所有活性化合物和大多数非活性化合物都被肾皮质的肾小管细胞以及肝脏的网状细胞和实质细胞摄取。虽然锥虫蓝给药1天后对肝脏和肾脏都有影响，但核糖核酸酶活性在第一个器官中仅增加约3天，而在第二个器官中至少增加一个月。然而，重复给予锥虫蓝可使肝脏酶活性增加至少9天。锥虫蓝给药后血清核糖核酸酶活性降低。乙硫氨酸与锥虫蓝一起给药可显著阻断该染料对肝脏核糖核酸酶活性的影响；同时给予蛋氨酸可部分逆转抗代谢物的作用。这表明锥虫蓝可诱导肝脏中核糖核酸酶的从头合成。乙硫氨酸对肾脏核糖核酸酶对锥虫蓝反应的作用虽不显著但仍有意义；鉴于血浆酶可能被肾脏摄取，这一发现的解释必须推迟。结合所用化合物的结构特异性机制、染料的细胞定位及其对肝脏和肾脏核糖核酸酶的作用机制对结果进行了讨论。
