Davidoff A N, Mendelow B V
Department of Haematology, School of Pathology, South African Institute for Medical Research, Johannesburg.
Exp Hematol. 1993 Mar;21(3):456-60.
This study investigated and compared the cytokinetic, phenotypic and molecular effects elicited in HL-60 human leukemic cells by low doses (0.6 microM) of 3 closely related, substituted purines, puromycin (PM), puromycin aminonucleoside (PAN) and 6-dimethylaminopurine (6-DMAP). PM, but not 6-DMAP or PAN, inhibited [14C]leucine incorporation, induced a time-related cytotoxic effect, a G2-arrest, a metaphase-mitotic-arrest, apoptosis and c-myc mRNA superinduction. PAN and 6-DMAP exerted no detectable morphological or cytokinetic effects, although exposure to these drugs resulted in downregulation of c-myc mRNA levels. We suggest that the specific effects exerted by PM relate to the generation of nascent peptidyl-PM complexes by PM, but not by 6-DMAP or PAN.
本研究调查并比较了低剂量（0.6微摩尔）的3种密切相关的取代嘌呤——嘌呤霉素（PM）、嘌呤霉素氨基核苷（PAN）和6-二甲基氨基嘌呤（6-DMAP）对HL-60人白血病细胞产生的细胞动力学、表型和分子效应。PM可抑制[14C]亮氨酸掺入，诱导与时间相关的细胞毒性效应、G2期阻滞、中期-有丝分裂期阻滞、凋亡以及c-myc mRNA超诱导，而6-DMAP或PAN则无此作用。尽管暴露于这些药物会导致c-myc mRNA水平下调，但PAN和6-DMAP未产生可检测到的形态学或细胞动力学效应。我们认为，PM产生的特定效应与PM生成新生肽基-PM复合物有关，而6-DMAP或PAN则不会。
