INDUCTION OF RESISTANCE TO MELARSENOXIDE CYSTEAMINE (MEL CY) IN TRYPANOSOMA-BRUCEI-BRUCEI

A population of Trypanosoma brucei brucei with reduced sensitivity to melarsenoxide cysteamine (Mel Cy) was produced in immunosuppressed mic e using subcurative drug treatment. Melarsenoxide cysteamine resistanc e was stable after cyclical transmission through Glossina morsitans ce ntralis. In vitro, the bloodstream forms showed 15-fold higher values for the minimal inhibitory concentration as compared with the parental clone. Cross-resistance could be determined with another arsenical dr ug, melarsoprol (14-fold) and to two different diamidines (diminazene aceturate: 47-fold; pentamidine methanesulphonate: 34-fold), but not t o suramin. When cells were transformed to procyclic forms and tested i n vitro, the sensitivity of the resistant population to melarsenoxide cysteamine was only 6-fold lower than that of the parent, but comparat ively high cross-resistance could be shown to other drugs (melarsoprol : 85-fold; pentamidine methanesulphonate: 17-fold; quinapyramine sulph ate: 40-fold). Selection of the resistant trypanosomes from non-resist ant ones was possible under pentamidine methanesulphonate pressure in cell culture.