Drug effects on the fine structure of trypanosoma rhodesiense: Diamidines

Abstract

Three aromatic diamidine trypanocides, Berenil, hydroxystilbamidine and pentamidine, have been found to show similar and specific lesions in the fine structure of Trypanosoma rhodesiense taken from infected mice 5 to 6 hours after treatment with a curative dose of the drug. The primary effect of all 3 compounds was to disintegrate selectively the kinetoplast DNA core into round dense granules and micro-fibrils; the normal core is a uniform fibrillar lamellar structure. There was no effect on the nucleus. Possible causes for this selectivity are discussed in relation to the properties of kinetoplast DNA and the behaviour of trypanocides with an affinity for kinetoplast localization. Later effects of pentamidine include aggregation and loss of ribosomes, nucleolar dispersion, and formation of cytoplasmic membrane whorls intimately related to bodies resembling myelin figures. The latter may have been formed as a result of lysosomal enyme action, as large numbers of “empty” lysosomes were present. Lysosomal function is also discussed in relation to drug uptake and interaction, with some speculation on the rôle of lysosomes in drug-induced intracellular lesions in the trypanosome.