Steinberg S E, Campbell C L, Rabinovitch P S, Hillman R S
Blood. 1980 Mar;55(3):501-4.
Cultures of Friend erythroleukemia cells were subjected to the antibiotics trimethoprim (T) and sulfamethoxazole (S) at levels equal to or below the usual therapeutic range. At T 8 microgram/ml and S 40 microgram/ml, cell growth was arrested, cells appeared megaloblastic, and the examination of cell-cycle distribution by flow microfluorimetry revealed arrest in S phase. With a tenfold reduction in drug levels (T, 08 microgram/ml; S, 4 microgram/ml) cell growth was less markedly inhibited, morphology remained megaloblastic, and S-phase block was still dramatic. A further tenfold reduction (T, 0.08 microgram/ml; S, 0.4 microgram/ml), well below effective antibacterial levels, allowed normal cell growth and morphology but DNA synthesis was still inhibited. Additions of folinic acid at 100 ng/ml averted all drug effects. Thus T/S can affect cell replication even at levels well below those usually employed and could prolong the rate of recovery of hematopoietic cells in the myelosuppressed patient.
将弗瑞德红白血病细胞培养物置于等于或低于通常治疗范围水平的抗生素甲氧苄啶（T）和磺胺甲恶唑（S）中。在T为8微克/毫升和S为40微克/毫升时，细胞生长停止，细胞呈现巨幼细胞样，通过流式微量荧光测定法检测细胞周期分布显示细胞停滞于S期。药物水平降低十倍（T为0.8微克/毫升；S为4微克/毫升）时，细胞生长受到的抑制不太明显，形态仍为巨幼细胞样，S期阻滞仍然显著。再降低十倍（T为0.08微克/毫升；S为0.4微克/毫升），远低于有效抗菌水平，细胞生长和形态恢复正常，但DNA合成仍受抑制。添加100纳克/毫升的亚叶酸可消除所有药物作用。因此，即使在远低于通常使用水平的情况下，T/S仍可影响细胞复制，并可能延长骨髓抑制患者造血细胞的恢复速度。
