Kinetoplasts play an important role in the drug responses of Trypanosoma brucei.
Trypanosoma brucei E164 and a dyskinetoplastic derivative, Dysk164, were injected into mice that were treated subsequently with methylglyoxal-bis-guanylhydrazone, berenil, ethidium bromide, and acriflavine. Additionally, parasites were photoaffinity labeled with ethidium monoazide to effect covalent drug attachment prior to injection into animals. In all cases, killing of animals with E164 was blocked by the drug treatment, whereas killing due to Dysk164 was not. These findings are consistent with the view that the intact kinetoplast plays an essential role in the action of these drugs.
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Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston 77555-1031, USA.
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D000167:Acriflavine / Q000494:pharmacology; D000818:Animals; D001386:Azides / Q000494:pharmacology / Q000528:radiation effects; D004133:Diminazene / Q000031:analogs & derivatives / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance / Q000235:genetics; D004996:Ethidium / Q000494:pharmacology; D005260:Female; D008027:Light; D051379:Mice; D008928:Mitochondria / Q000187:drug effects* / Q000235:genetics; D008935:Mitoguazone / Q000494:pharmacology; D009154:Mutation; D018512:Parasitemia / Q000188:drug therapy; D014344:Trypanocidal Agents / Q000494:pharmacology*; D014346:Trypanosoma brucei brucei / Q000187:drug effects* / Q000235:genetics; D014353:Trypanosomiasis, African / Q000188:drug therapy*
D001386:Azides; D014344:Trypanocidal Agents; D000167:Acriflavine; C014535:8-azidoethidium; D004996:Ethidium; C003915:diminazene aceturate; D008935:Mitoguazone; D004133:Diminazene