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During differentiation of the dividing epimastigote to the non-dividing metacyclic trypomastigote form of the parasitic protozoan Trypanosoma cruzi there is a marked reduction in the rate of synthesis of the major proteins alpha- and beta-tubulin. Our results indicate that the control of synthesis of these proteins during the differentiation event is exerted at the level of alpha- and beta-tubulin mRNA accumulation.

Taxol, an experimental antitumor agent and stabilizer of microtubules, inhibits in vitro replication of the human pathogenic hemoflagellate Trypanosoma cruzi. Micromolar concentrations of the drug prevent the completion of cell division in these organisms but allow the multiplication of cell organelles such as the nucleus, kinetoplast, and flagellum. The result is the formation of motile organisms that have extra organelles but cannot fully replicate. Division proceeds to a relatively fixed locus on the long axis of the organism, suggesting the presence of a specific affected structure or function at this site. It is postulated that taxol produces these effects by stabilizing a portion of the microtubular cytoskeleton of T. cruzi.

When Trypanosoma cruzi are treated with Berenil, a trypanocide, their kinetoplast DNA contains an increased proportion of double-branched circular molecules. These replicating molecules have closed-circular template strands; their decrease in density when complexed by ethidium bromide in a cesium chloride gradient is proportional to the length of the replicated segments. Replication seems to be blocked at specific points, which are equidistantly spaced along the circular kinetoplast DNA molecules. Analysis of about 800 replicating forms showed that the lengths of the replicated branches are not distributed at random, but into several populations, which correspond to multiples of 15% of the total contour length of 0.5 mum. This distribution evokes a discontinuous replication process. The problem of whether kinetoplast DNA is synthesized by successive replication units, or whether and how Berenil might induce specific blocking of DNA replication, is discussed.