Hori S, Kayanuma K, Ohtani S, Sugiura H, Tsubaki T
J Toxicol Sci. 1987 May;12(2):97-109. doi: 10.2131/jts.12.97.
The inhibitory effects of 5-chloro-7-iodo-8-hydroxy-quinoline (clioquinol), methylmercuric chloride and 4-hydroxyaminoquinoline-N-oxide(4-HAQO) on DNA, RNA and protein syntheses in the neonatal rat superior cervical ganglion (SCG) were studied in relation to the action of mouse 2.5S nerve growth factor (NGF), using organ cultures. RNA and protein syntheses in SCG were stimulated approximately 3- and 2-fold, respectively, by NGF (1 microgram/ml), but the DNA synthesis was only slightly or not at all stimulated. Methylmercuric chloride and 4-HAQO dose-dependently inhibited DNA, RNA and protein syntheses, either in the presence or in the absence of NGF. On the other hand, clioquinol (up to 100 microM) slightly or not at all inhibited RNA synthesis in the absence of NGF; however, it did abolish the NGF-induced stimulation of RNA synthesis in the presence of NGF. The DNA and protein syntheses were dose-dependently inhibited by clioquinol, either in the presence or in the absence of NGF. We conclude from this study that the interaction between clioquinol and the functions of NGF raises the question of a possible toxicity of the drug on specific neurons.
利用器官培养技术,研究了5-氯-7-碘-8-羟基喹啉(氯碘羟喹)、甲基氯化汞和4-羟基氨基喹啉-N-氧化物(4-HAQO)对新生大鼠颈上神经节(SCG)中DNA、RNA和蛋白质合成的抑制作用,并探讨了其与小鼠2.5S神经生长因子(NGF)作用的关系。NGF(1微克/毫升)可使SCG中的RNA和蛋白质合成分别增加约3倍和2倍,但对DNA合成仅有轻微刺激或无刺激作用。无论有无NGF存在,甲基氯化汞和4-HAQO均呈剂量依赖性抑制DNA、RNA和蛋白质合成。另一方面,在无NGF时,氯碘羟喹(高达100微摩尔)对RNA合成仅有轻微抑制或无抑制作用;然而,在有NGF存在时,它确实消除了NGF诱导的RNA合成刺激。无论有无NGF存在,氯碘羟喹均呈剂量依赖性抑制DNA和蛋白质合成。我们从这项研究中得出结论,氯碘羟喹与NGF功能之间的相互作用引发了该药物对特定神经元可能具有毒性的问题。