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Studies on the Carcinogenicity of the Glucuronides of N-Hydroxy-2-acetylaminofluorene and N-2-Fluorenylhydroxylamine in the Rat¹

Veterans Administration Hospital [C. C. I., R. W.], Memphis 38104, and Department of Biochemistry, University of Tennessee [C. C. I.], Memphis, Tennessee 38103

The O-glucuronide of N-hydroxy-2-acetylaminofluorene was assayed for carcinogenicity by s.c. injection in female Holtzman rats. No tumors were produced in animals in which tricaprylin was used as a vehicle for administration of N-hydroxy-2-acetylaminofluorene-O-glucuronide as a suspension. However, when injected s.c. as a solution in 0.9% NaCl, N-hydroxy-2-acetylaminofluorene-O-glucuronide induced a total of nine tumors in 16 rats: one sarcoma at the site of injection, four mammary carcinomas, three ear duct carcinomas, and one liver carcinoma. The influence of solvent for assay of carcinogenicity was demonstrated also in experiments with tricaprylin and 0.9% NaCl as vehicles for administration of the aglycone, N-hydroxy-2-acetylamino-fluorene. When N-hydroxy-2-acetylaminofluorene was given as a suspension in tricaprylin, 35 tumors were produced in 16 rats, whereas, when it was administered as a suspension in 0.9% NaCl, 20 tumors were found in 16 rats. Only two tumors, a sarcoma at the site of injection and a mammary carcinoma (both in the same rat), were found in 16 rats that received s.c. injections of the N-2-fluorenylhydroxylamine-O-glucuronide.

¹ Supported by the Veterans Administration and by USPHS Research Grant CA-05490 from the National Cancer Institute.

Received 5/ 6/71. Accepted 6/25/71.