Substituted purines elicit differential cytokinetic, molecular and phenotypic effects in HL-60 cells

• Published in: Experimental hematology Vol. 21; no. 3; p. 456
• Main Authors: Davidoff, A N, Mendelow, B V
• Format: Journal Article
• Language: English
• Published: Netherlands 01.03.1993
• Subjects: Adenine - analogs & derivatives; Adenine - analysis; Adenine - chemistry; Adenine - pharmacology; Carbon Radioisotopes; Cell Cycle - drug effects; DNA, Neoplasm - genetics; Dose-Response Relationship, Drug; Down-Regulation; Flow Cytometry; Humans; Kinetics; Leucine - metabolism; Leukemia, Promyelocytic, Acute - pathology; Phenotype; Proto-Oncogene Proteins c-myc - genetics; Proto-Oncogene Proteins c-myc - metabolism; Purines - analysis; Purines - chemistry; Purines - pharmacology; Puromycin - analysis; Puromycin - chemistry; Puromycin - pharmacology; Puromycin Aminonucleoside - analysis; Puromycin Aminonucleoside - chemistry; Puromycin Aminonucleoside - pharmacology; RNA, Messenger - analysis; RNA, Messenger - genetics; Time Factors; Tumor Cells, Cultured - drug effects; Tumor Cells, Cultured - pathology
• ISSN: 0301-472X

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.