ABSTRACT
Antrycide is an aminoquinaldine whose inhibitory action on the growth of Trypanosoma and Crithidia is not fully understood at the cellular level. The growth of Amoeba discoides in concentrations of antrycide between 0.5 and 2 microgram/ml was reduced considerably, while cells failed to divide in 4 microgram/ml. The effects on growth rate were reversible at least up until 7 days in antrycide. In order to assess the action of this synthetic drug on RNA synthesis in amoebae, the pattern of synthesis in normal cells was investigated using polyacrylamide gel electrophoresis. The profile of high molecular weight RNAs observed depended on the length of time in [3H]uridine, and was only fully developed after 66 h, when 5 peaks could be seen. The relative molecular weights of these peaks (I--V) were 2.45, 1.55, 1.13, 0.8 and 0.52 X 10(6) Daltons respectively. Those of 1.55 and 0.8 X 10(6) corresponded to ribosomal RNAs, the identity of the other peaks is unknown. After growth in 2 microgram/ml antrycide for 4 days, no high molecular weight RNA was found. Use of [14C]adenine/[3H]uridine showed that after 17 h in antrycide there was a loss of ribosomal RNA and increased levels of low molecular weight RNAs, due either to lack of synthesis or to degradation of newly synthesized material. Incorporation of [3H]leucine into hot acid-precipitable protein was inhibited in antrycide-treated cells by at least 50%. A possible explanation of the effect of antrycide on A. discoides was the inhibition of mRNA synthesis for ribosomal proteins, leading to degradation of newly synthesized rRNA. Reduced growth would continue on pre-existing ribosomes and previously synthesized long-lived mRNAs.
