Specific inhibition of the differentiation of Trypanosoma cruzi.
The morphological transformation of Trypanosoma cruzi amastigotes was studied in both mammalian cells and an extracellular differentiation system. Inhibitors of ADP-ribosyl transferase were found to block differentiation in both cases, without affecting proliferation. The inhibitory effect was reversible and was not observed with chemical analogues that do not inhibit ADP-ribosyl transferase. As inhibitors of ADP-ribosyl transferase have recently been shown to block the differentiation of several cell types from vertebrates (Farzaneh, F., R. Zalin, D. Brill, and S. Shall, 1982, Nature (Lond.), 300:362-366; Johnstone, A. P., and G. T. Williams, 1982, Nature (Lond.), 300:368-370), our results suggest that the enzyme is of general importance in eucaryotic differentiation both in multicellular and unicellular organisms. In addition, since the compounds can block T. cruzi differentiation inside mammalian cells, these results suggest that it may be possible to exploit such inhibition in a new and potentially powerful approach to the chemotherapy of several important parasitic diseases.
D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D046508:Culture Techniques; D008675:Metamorphosis, Biological / Q000187:drug effects*; D051379:Mice; D009536:Niacinamide / Q000031:analogs & derivatives / Q000494:pharmacology; D009713:Nucleotidyltransferases / Q000037:antagonists & inhibitors*; D011065:Poly(ADP-ribose) Polymerases; D013997:Time Factors; D014349:Trypanosoma cruzi / Q000254:growth & development*
D001549:Benzamides; D009536:Niacinamide; C024785:5-methylnicotinamide; D011065:Poly(ADP-ribose) Polymerases; D009713:Nucleotidyltransferases; C025159:3-methoxybenzamide