The effect of some platinum compounds on the activity of the CTP synthetase of Ehrlich ascites tumor cells: in vitro and in vivo studies.
The present work investigates the effect of cis-DDP (DDP, diamminedichloroplatinum(II)), trans-DDP, SPC (spermine platinum(II) complex), and K2PtCl4 on the activity of the CTP synthetase in the cytosol of Ehrlich ascites tumor cells. To study their in vitro effect, the platinum compounds were supplemented to the incubation mixture for the enzyme assay. A concentration dependent inhibition of the CTP synthetase was found which was strongest in the case of trans-DDP. When ascites cells collected from mice, pretreated in vivo with platinum compounds, were used, the enzyme assay showed that the inhibition is strongest in the case of cis-DDP and K2PtCl4 (about 90% inhibition). This distinct inhibitory effect of the platinum compounds in the present experiments may be explained with the metabolic conversions of the compounds in the organism to their more active forms and/or with the inhibition of the protein biosynthesis under their influence because the lifetime of the CTP synthetase is short. This last assertion is proved in this work by control experiments with the antibiotic cycloheximide, which is an inhibitor of the protein biosynthesis.
Ganeva
R L
RL
Institute of Molecular Biology, Bulgarian Academy of Sciences, Sofia.
Spassovska
N C
NC
Genchev
D D
DD
D000818:Animals; D019731:Carbon-Nitrogen Ligases; D002286:Carcinoma, Ehrlich Tumor / Q000201:enzymology* / Q000473:pathology; D003600:Cytosol / Q000201:enzymology; D066298:In Vitro Techniques; D008025:Ligases / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D010984:Platinum / Q000494:pharmacology*
D010984:Platinum; D008025:Ligases; D019731:Carbon-Nitrogen Ligases; C019951:CTP synthetase