Goncharova S A, Frankfurt O S
Cell Tissue Kinet. 1976 Jul;9(4):333-40. doi: 10.1111/j.1365-2184.1976.tb01281.x.
The influence of methotrexate (MTX) on the proliferative activity of cells in different phases of cell cycle has been studied. MTX (5 mg/kg) was injected i.p. 3 days after the inoculation of 5 X 10(6) leukemia cells, into F1 (DBA X C57 BL) mice. It was shown that MTX causes degeneration of cells, being in G1- as well as in S-phase at the time of drug injection. Incorporation of 3H-TdR was suppressed for a period ranging from 2 to 12 hr after MTX administration, which is demonstrated by the decrease in the number of grains per cell. The number of cells labeled after 3H-TdR injection was also sharply decreased during this period. For a period of 3 until 15 hr after MTX administration the mitotic index decreased significantly as a result of inhibition of DNA synthesis. The blocking of the G1-S transition was evident during 4 hr after MTX. Thereafter the G1-S transition proceeds at a rate which is practically equal to that for nontreated controls. MTX did not inhibit transition to mitosis of cells being in G2-phase and in a very late S-phase at the time of drug injection. The sensitivity of G1-cells to the cytocidal effect of MTX shows that for L1210 leukemia cells MTX can be classified as a cycle-specific drug killing both G1-and S-cells rather than S-phase specific agent with self-limitation.
研究了甲氨蝶呤（MTX）对细胞周期不同阶段细胞增殖活性的影响。在给F1（DBA×C57 BL）小鼠接种5×10⁶个白血病细胞3天后，腹腔注射MTX（5 mg/kg）。结果表明，MTX导致在注射药物时处于G1期和S期的细胞发生变性。MTX给药后2至12小时内，³H-TdR的掺入受到抑制，这表现为每个细胞的银粒数减少。在此期间，³H-TdR注射后标记的细胞数量也急剧减少。MTX给药后3至15小时内，由于DNA合成受到抑制，有丝分裂指数显著下降。MTX给药后4小时内，G1-S期转换的阻断明显。此后，G1-S期转换以与未处理对照组实际相等的速率进行。MTX不抑制在注射药物时处于G2期和非常晚期S期的细胞向有丝分裂的转换。G1期细胞对MTX杀细胞作用的敏感性表明，对于L1210白血病细胞，MTX可被归类为一种周期特异性药物，既能杀死G1期和S期细胞，而不是具有自我限制作用的S期特异性药物。
