Effect of mitomycin C, actinomycin D, and pyrimidine analogs on the growth rate, protein and nucleic acid synthesis, and on the viability of Trypanosoma cruzi

Abstract

The effects of pyrimidine analogs, mitomycin C, and actinomycin D on the in vitro growth of Trypanosoma cruzi as well as on the biosynthesis of the protein, RNA, and DNA are studied. While iodo and bromouracil deoxyriboside exert little inhibitory effect, fluorouracil deoxyriboside does inhibit strongly the DNA synthesis and, as an after effect, the RNA and protein synthesis. The cells thus inhibited seem to be alive, but few of them are viable. Mytomycin C does inhibit DNA and protein synthesis after 6 hours of incubation, inhibiting RNA synthesis a little later. Actinomycin D, on the other hand, leads up to an almost immediate blockage of the RNA synthesis followed by inhibition of DNA and protein synthesis. The cells cultivated in the presence of actinomycin D appear to lose the multiplication capacity as found by the negligible incorporation of thymidine into DNA. Such cells seem to be devoid of infectivity capacity but apparently they protect mice against a challenge with virulent strain of T. cruzi. The significance of these results as well as their importance to the problem of vaccination against Chagas' disease are discussed.