Studies with the schistosomacide hycanthone: Inhibition of macromolecular synthesis and its reversal

The new schistosomacide, hycanthone, was studied with regard to its effects upon macromolecular synthesis in mammalian (HeLa) cells. At concentrations as low as 5 × 10^-8 M, hycanthone reduces plating efficiency of HeLa cells. At 10^-6M, effects on population growth are evident by the second generation. At 5 × 10^-6 M, RNA synthesis is markedly depressed while DNA and protein synthesis are relatively unaffected. New ribosomal RNA synthesis is rapidly inhibited by hycanthone at 5 × 10^-6 M, and its processing is markedly delayed. During hycanthone inhibition 28S RNA does not appear in the cytoplasm. Hycanthone inhibition was shown to be readily reversible by washing the cells in fresh medium. The case with which inhibition can be reversed in vitro suggests that it may be necessary to maintain blood levels of this compound if permanent eradication of schistosomal infection is to be attained. Further work must be done to establish this point.