Kim I K, Aksamit R R, Cantoni G L
J Biol Chem. 1982 Dec 25;257(24):14726-9.
3-Deazaaristeromycin (100 microM) is cytostatic for the RAW264 mouse macrophage cell line. In cells incubated with 3-deazaaristeromycin, Cell replication is effectively stimulated by 0.5 microM homocysteine thiolactone and no further stimulation occurs at concentrations of homocysteine thiolactone greater than 50 microM. Cell replication occurs when homocysteine thiolactone is administered either simultaneously with, or 4 days after, the administration of 3-deazaaristeromycin. In the presence of 3-deazaaristeromycin, cell replication also occurs when either folate (10 to 100 microM) or hypoxanthine and thymidine are included in the medium. Incorporation of [14C]formate into trichloroacetic acid-precipitable material is inhibited when cells are incubated with 3-deazaaristeromycin, and this inhibition is partially reversed by inclusion of either homocysteine thiolactone or folate in the medium. Experiments showed that adenosylhomocysteine hydrolase is inhibited to the same extent after the cells have been incubated for 4 days with either 3-deazaaristeromycin or 3-deazaaristeromycin and homocysteine thiolactone. The findings suggest that in cells incubated with 3-deazaaristeromycin, the formation of homocysteine from S-adenosylhomocysteine is insufficient for the regeneration of tetrahydrofolate for the synthesis of purines and pyrimidines.
3-去氮阿糖胞苷（100微摩尔）对RAW264小鼠巨噬细胞系具有细胞生长抑制作用。在用3-去氮阿糖胞苷孵育的细胞中，0.5微摩尔的同型半胱氨酸硫内酯可有效刺激细胞复制，而同型半胱氨酸硫内酯浓度大于50微摩尔时则不会产生进一步刺激。同型半胱氨酸硫内酯与3-去氮阿糖胞苷同时给药或在给药后4天给药时，细胞都会发生复制。在存在3-去氮阿糖胞苷的情况下，当培养基中含有叶酸（10至100微摩尔）或次黄嘌呤和胸腺嘧啶时，细胞也会发生复制。当细胞用3-去氮阿糖胞苷孵育时，[14C]甲酸掺入三氯乙酸沉淀物质的过程受到抑制，而培养基中加入同型半胱氨酸硫内酯或叶酸可部分逆转这种抑制作用。实验表明，细胞用3-去氮阿糖胞苷或3-去氮阿糖胞苷与同型半胱氨酸硫内酯孵育4天后，腺苷同型半胱氨酸水解酶受到的抑制程度相同。这些发现表明，在用3-去氮阿糖胞苷孵育的细胞中，S-腺苷同型半胱氨酸生成同型半胱氨酸的过程不足以再生用于嘌呤和嘧啶合成的四氢叶酸。
