The delayed cytotoxic effect of 6-mercaptopurine Characterization of the unbalanced growth in HeLa cells produced by 6-mercaptopurine

Abstract Pulse exposure to 6-mercaptopurine induced a delayed cytotoxic reaction in HeLa cells at concentrations 10–200 μM. Abortive proliferation occurred after lethal 6-mercaptopurine exposure. Unbalanced growth was an integral part of this delayed reaction. In connection with decrease in cell proliferation which followed 6-mercaptopurine treatment a gradual increase in cell size occurred. The initial aspect of the 6-mercaptopurine delayed reaction was characterized by decreases in DNA and RNA content per unit cell volume, while protein concentrations remain constant. However, in the later post-6-mercaptopurine exposure period the protein:cell volume ratios increased and nucleic acids accumulated. The increased content of DNA suggested that cells synthesized DNA without entering into mitosis and that dying cells were in late-S or G 2 phases prior to lysis. Thus, cell death was preceded by disturbance of cellular, nuclear and chromosomal divisions.