Substituted purines elicit differential cytokinetic, molecular and phenotypic effects in HL-60 cells.
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.
Davidoff
A N
AN
Department of Haematology, School of Pathology, South African Institute for Medical Research, Johannesburg.
Mendelow
B V
BV
D000225:Adenine / Q000031:analogs & derivatives / Q000032:analysis / Q000737:chemistry / Q000494:pharmacology; D002250:Carbon Radioisotopes; D002453:Cell Cycle / Q000187:drug effects; D004273:DNA, Neoplasm / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D005434:Flow Cytometry; D006801:Humans; D007700:Kinetics; D007930:Leucine / Q000378:metabolism; D015473:Leukemia, Promyelocytic, Acute / Q000473:pathology*; D010641:Phenotype; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D011687:Purines / Q000032:analysis / Q000737:chemistry / Q000494:pharmacology*; D011691:Puromycin / Q000032:analysis / Q000737:chemistry / Q000494:pharmacology; D011692:Puromycin Aminonucleoside / Q000032:analysis / Q000737:chemistry / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D013997:Time Factors; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000473:pathology
D002250:Carbon Radioisotopes; D004273:DNA, Neoplasm; D016271:Proto-Oncogene Proteins c-myc; D011687:Purines; D012333:RNA, Messenger; D011691:Puromycin; D011692:Puromycin Aminonucleoside; C001020:N(6),N(6)-dimethyladenine; D007930:Leucine; D000225:Adenine