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Fels Research Institute, Temple University School of Medicine, Philadelphia, Pennsylvania 19140 [D. S. R. S., S. R., J. Z., E. F.]; Department of Pathology, University of Toronto, Medical Sciences Building, Toronto, Ontario, Canada, M5S 1A8 [H. T., D. S. R. S., S. R., E. F.]; and Department of Pathobiology, School of Hygiene and Public Health, the Johns Hopkins University, Baltimore, Maryland 21205 [R. P. B., Y-N. C., E. B.]
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.
1 This investigation was supported in part by USPHS Grants CA-14689, CA-12218, CA-12227, CA-18251, and GM-16492 from the NIH and by a grant from the National Cancer Institute of Canada.
2 To whom requests for reprints should be addressed, at Department of Pathology, University of Toronto, Medical Sciences Building, 1 Kings College Circle, Toronto, Ontario, Canada, M5S 1A8.
Received 2/ 5/79. Accepted 8/10/79.
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