Induction of hepatic neoplastic lesions in mice with a single dose of hycanthone methanesulfonate after partial hepatectomy.
Experiments were designed to determine whether hycanthone methanesulfonate (1-([2-(diethylamino)ethyl]amino)-4-(hydroxymethyl)thioxanthen-9-one monomethanesulfonate), an antischistosomal drug, and its analog, IA-4-N-oxide (8-chloro-2-[2-(diethylamino)ethyl]-2H-[1]benzothiopyrano[4,3,2-cd]indazole 5-methanol monomethanesulfonate), will induce neoplastic lesions in the livers of mice not infected with Schistosoma mansoni. All the mice received a single i.m. injection of hycanthone methanesulfonate (76 mg/kg), IA-4-N-oxide (80 mg/kg), or an equivalent volume of the solvent, 0.9% NaCl solution, 42 hr after partial hepatectomy. Of the mice receiving hycanthone methanesulfonate and living 200 days or longer, hepatocellular carcinoma was seen in 11.5% and liver sarcoma was seen in 4.2%. This type of malignant neoplasm was not seen in the animals receiving either IA-4-N-oxide or 0.9% NaCl solution. In addition, mice receiving hycanthone methanesulfonate showed a significantly higher incidence of both type 1 (43% compared to 21% in controls) and type 2 (21% compared to 12% in controls) hepatocyte neoplasms. Mice receiving IA-4-N-oxide showed no increased incidence of neoplasms.
D000818:Animals; D006498:Hepatectomy; D006826:Hycanthone / Q000009:adverse effects*; D008113:Liver Neoplasms / Q000139:chemically induced* / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced; D008115:Liver Regeneration; D008297:Male; D051379:Mice; D011230:Precancerous Conditions / Q000139:chemically induced; D012513:Sarcoma, Experimental / Q000139:chemically induced; D013892:Thioxanthenes / Q000009:adverse effects*; D013997:Time Factors
D013892:Thioxanthenes; D006826:Hycanthone