HYCANTHONE-INDUCED HEPATIC CHANGES IN MICE INFECTED WITH SCHISTOSOMA MANSONI

¹ Departments of Pathology and of Pharmacology and Experimental Therapeutics, School of Medicine; Department of Pathobiology, School of Hygiene and Public Health, The Johns hopkins University, Baltimore, Maryland

Fifty-four to 104 weeks after infection of female mice with cercariae of Schistosoma mansoni, hepatic hyperplasia was observed in 29% of the animals. Cessation of egg production and elimination of the worms, brought about by the administration of the schistosomicidal drug SQ 18,506 55 days after infection, resulted in a lower incidence of hepatic hyperplasias. By contrast, administration of a single dose of hycanthone, another antischistosomal drug, produced a significant increase in the incidence of hepatic hyperplasia. Furthermore, in contrast to SQ 18,506-treated controls, the appearance of hepatocellular carcinomas was observed in hycanthone-treated infected mice, even after the adult worms had been killed and the deposition of eggs had been eliminated. In uninfected mice administration of a single dose of hycanthone produced neither hepatic hyperplasia nor hepatomas. It is concluded that the hepatic hyperplasia, induced by the deposition of schistosome eggs in the liver and enhanced by hycanthone, is a predisposing factor for a hepatocarcinogenic effect of this drug.