Cytotoxicity of dichloromethane diphosphonate and of 1-hydroxyethane-1,1-diphosphonate in the amoebae of the slime mould Dictyostelium discoideum. A 31P NMR study.
Two pyrophosphate analogues, dichloromethane diphosphonate (Cl2MDP), and 1-hydroxyethane-1,1-diphosphonate (EHDP), at concentrations of 0.5-1 mM, efficiently inhibited the growth of amoebae of the slime mould Dictyostelium discoideum. Cell viability decreased markedly upon incubation with the diphosphonates. The mechanism of toxicity was investigated by in vivo 31P NMR spectroscopy and the formation of analogues of ATP [adenosine 5'-(beta, gamma-dichloromethane triphosphate) and adenosine 5'-(beta, gamma-1-hydroxyethane triphosphate)] was demonstrated. These two compounds were identified from their 31P NMR spectra in perchloric acid extracts prepared from amoebae poisoned with Cl2MDP or EHDP and may have been synthesized by reversible pyrophosphate exchange catalysed by cytosolic aminoacyl-tRNA synthetases.
Pelorgeas
S
S
Département de Biologie Moléculaire et Structurale, Groupement CEA-CNRS-INSERM-UJF, Grenoble, France.
Martin
J B
JB
Satre
M
M
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004002:Clodronic Acid / Q000737:chemistry / Q000633:toxicity*; D004023:Dictyostelium / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D012968:Etidronic Acid / Q000737:chemistry / Q000633:toxicity*; D008274:Magnesium / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D009711:Nucleotides / Q000096:biosynthesis; D010758:Phosphorus; D010766:Phosphorylation
D009711:Nucleotides; D004002:Clodronic Acid; D010758:Phosphorus; D008274:Magnesium; D012968:Etidronic Acid