Resistance to Purified Acriflavin in Leishmania tarentolae

THE mechanism by which purified acriflavin (3,6-diamino-N-methyl acridinium chloride) affects haemoflagellates has long been a matter of speculation. Available evidence indicates that the dye may interfere with replication of kinetoplast DNA^1–9, with mitochondrial function^{1, 9} and with certain cytoplasmic enzymes¹⁰. In preparations stained with Feulgen or Giemsa, the kinetoplast appears as the darkly stained granule near the base of the flagellum (Fig. 1). Electron microscopy and biochemical techniques have shown that it contains DNA surrounded by a double membrane that is continuous with the mitochondrial system^{4, 6–8, 11–17}. When acriflavin is added to cultures of Leishmania tarentolae, fluorescence from the dye appears in the kinetoplast¹. Several cell generations later, the kinetoplast disappears in many haemoflagellates, dividing in the presence of the dye (as judged by Giemsa or Feulgen staining^{1, 2, 5–7, 13, 18, 19}), leading to dyskinetoplasia⁶. The amount^1–3 and fine structure^{2, 6, 7, 9, 13} of kinetoplast DNA are, moreover, altered. Tritiated thymidine no longer appears in the kinetoplast region when it is examined by light¹ and electron microscope⁹ autoradiography.