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The Carcinogenic Activity of Some 5-Nitrofuran Derivatives in the Rat^1,2,

Division of Clinical Oncology [J. E. M., J. M. P.] and Department of Pathology [J. J. L.] University of Wisconsin Medical School, Madison, Wisconsin 53706, and Abbott Laboratories, Scientific Divisions, North Chicago, Illinois 60064 [R. J. S.]

Three 5-nitrofuran derivatives showed carcinogenic activity when fed to female Holtzman rats at levels of 0.1 to 0.3% in a commercial diet for up to 44.5 weeks, while 2 other 5-nitrofuran derivatives and 5,5-diphenylhydantoin were inactive. Formic acid 2-[4-(5-nitro-2-furyl)-2-thiazolyl]-hydrazide induced benign and malignant tumors of the mammary glands, adenomas or adenocarcinomas of the kidney, adenocarcinomas of the intestine, and carcinomas of the external auditory canal. 5-Nitro-2-furaldehyde semicarbazone produced only mammary tumors which were histologically benign. Acetone [4-(5-nitro-2-furyl)-2-thiazolyl]-hydrazone induced multiple squamous papillomas of the nonglandular forestomach. 5-Nitro-2-furanmethandiol diacetate and 1-[(5-nitrofurfurylidene)amino] hydantoin were inactive.

These compounds were tested on the hypothesis that the 5-nitrofuran moiety might have carcinogenic activity. Since 2 of the nitrofurans were not carcinogenic, however, the possibility that the observed carcinogenic activity might have been due to the hydrazine or thiazole moieties also is discussed.

¹ Supported in part by a grant from the American Cancer Society and by Contract PH 43 66 888 from the National Cancer Institute.

² The data reported here are taken from a thesis submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy by J. Emory Morris, University of Wisconsin, 1966.

³ Present address: Department of Chemistry, State University College at Brockport, Brockport, New York 14420.

⁴ Present address: Division of Experimental Therapy, Abbott Laboratories, North Chicago, Illinois 60064.

⁵ Present address: McHenry Medical Group and Hospital, McHenry, Illinois 60050.

Received 5/15/68. Accepted 3/14/69.