Inhibition of growth and of thymidine incorporation into DNA in Tetrahymena by chlorpromazine, pimozide and penfluridol.
The antipsychotic drugs chlorpromazine, pimozide, and penfluridol caused a 50% inhibition of growth of Tetrahymena at concentrations of 4.5, 5.5, and 1.5 microM, respectively. The degree of growth inhibition was dependent on the concentration of cells; higher drug concentrations were needed to produce inhibition of denser cell cultures. Binding studies with penfluridol showed that 50% growth inhibition resulted when approximately 50 mumoles of drug were bound per 10(6) cells. A 20-min preincubation of cells with chlorpromazine (14.7 microM) inhibited DNA synthesis by 46%, and with penfluridol (4 microM) DNA synthesis was inhibited by 27%. The incorporation of labeled thymidine into the thymidine triphosphate pool was inhibited by chlorpromazine but not by penfluridol, indicating that the drugs produce their growth inhibitory effects by different mechanisms. TDP kinase activity was demonstrated in a particle-free fraction of the cells. Its enzymatic activity was not affected by added chlorpromazine, penfluridol, or calmodulin, suggesting that inhibition of DNA synthesis by these drugs may be a consequence of growth inhibition.
D000818:Animals; D002746:Chlorpromazine / Q000494:pharmacology*; D004247:DNA / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D010395:Penfluridol / Q000378:metabolism / Q000494:pharmacology*; D010868:Pimozide / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology*; D013769:Tetrahymena pyriformis / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D013936:Thymidine / Q000378:metabolism; D013942:Thymine Nucleotides / Q000378:metabolism*
D010880:Piperidines; D013942:Thymine Nucleotides; D010868:Pimozide; D010395:Penfluridol; D004247:DNA; D002746:Chlorpromazine; D013936:Thymidine