Matsui T, Watanabe Y, Taketo A
Department of Health Information, Fukui Prefectural Institute of Public Health, Japan.
Anticancer Res. 1999 Jul-Aug;19(4B):3037-44.
Human neuroblastoma cells (KP-N-RT(BMI) treated with thymidine underwent morphological differentiation, as revealed by the extension of neurites. The morphological differentiation was caused by deoxyadenosine as well, but not by thymine or deoxyribose. The neurite-extending effect of thymidine was counteracted by deoxycytidine, indicating that inhibition of ribonucleotide reductase was involved. Similar morphological change was indeed brought about by hydroxyurea, a specific inhibitor of the enzyme. Azidothymidine and dideoxythymidine were also effective in induction of neurite extension, suggesting that inhibition of DNA replication, rather than the reductase per se, is responsible for the induction of neurite extension. Supporting this notion, various inhibitors of DNA synthesis induced the morphological differentiation of the cells. Although a-amanitin and cycloheximide were suppressive, actinomycin D promoted the thymidine-induced neurite extension. Morphological changes caused by thymidine were similar to those induced by cyclic AMP, rather than retinoic acid. Intracellular cAMP content was however not increased by the thymidine treatment.
用胸苷处理的人神经母细胞瘤细胞（KP-N-RT(BMI)）发生了形态学分化，这可通过神经突的延长来体现。脱氧腺苷也能引起形态学分化，但胸腺嘧啶或脱氧核糖则不能。胸苷的神经突延长作用被脱氧胞苷抵消，这表明其涉及核糖核苷酸还原酶的抑制。该酶的特异性抑制剂羟基脲确实能引起类似的形态学变化。叠氮胸苷和双脱氧胸苷在诱导神经突延长方面也有效，这表明是DNA复制的抑制而非还原酶本身导致了神经突延长。各种DNA合成抑制剂能诱导细胞发生形态学分化，这支持了这一观点。虽然α-鹅膏蕈碱和环己酰亚胺具有抑制作用，但放线菌素D能促进胸苷诱导的神经突延长。胸苷引起的形态学变化与环磷酸腺苷诱导的相似，而非视黄酸诱导的。然而，胸苷处理并未使细胞内的环磷酸腺苷含量增加。
