Long-term hepatocellular effects of hycanthone and of two other anti-Schistosomal drugs in mice infected with Schistosoma mansoni.

In confirmation of an earlier study, it was found that in mice infected with Schistosoma mansoni hepatocellular carcinomas are induced by hycanthone, an antischistosomal drug and potent frameshift mutagen. In addition, a high incidence 1) of micronodular hepatocellular whirling lesions with increased basophilia, 2) of other proliferative areas of altered cellularity and 3) of precancerous nodules was found in the livers of schistosome-infected mice treated with hycanthone. A dosage schedule of hycanthone which was too small to have any significant chemotherapeutic effect in mice (3 X 3 mg/kg) was sufficient to induce a statistically highly significant incidence of micronodular lesions and of precancerous nodules. Hence, the hepatic tissue proved more susceptible to low doses of this drug than the parasite. No significant hepatocarcinogenic effects or other hepatocellular changes were induced by chemotherapeutically effective doses of two related equipotent antischistosomal compounds, a chloroindazole analog of hycanthone, IA-4, and the tetrahydroquinoline derivative, oxamniquine.