Effect of hycanthone administered in vivo upon the incorporation of radioactive precursors into macromolecules of Schistosoma mansoni

Mice infected with Schistosoma mansoni were treated with hycanthone or with 8-chloro-2[2-(diethylamino)ethyl]-2H-[1]benzothiopirano-[4,3, 2-cd]-indazole-5-methanesulphonate (IA-4). Schistosomes were obtained by perfusion at various times after drug administration and tested for their ability to incorporate radioactive precursors of DNA, RNA and protein. In adult worms, male or female, the incorporation of radioactive thymidine was severely and irreversibly inhibited after treatment with either drug. Uridine and leucine incorporations were also inhibited, though to a lesser extent. On the contrary, the synthetic activities of immature worms were unaffected by hycanthone and only partially or temporarily depressed by IA-4. Hycanthone-resistant schistosomes, when tested between 1 and 7 days after treatment, showed a pattern of precursor incorporation which was virtually identical to that of untreated worms. These results are consistent with the hypothesis that hycanthone and IA-4 may kill schistosomes by interfering with their nucleic acid synthesis.