1. The carcinogenic activities for the rat of 4-acetylaminobiphenyl, N,N′-diacetylbenzidine, and eighteen related compounds have been investigated. The compounds were administered orally for 8–10 months.

  2. Under these conditions 4-acetylaminobiphenyl induced a high incidence of adenocarcinomas of the mammary gland in female rats and small numbers of adenocarcinomas of the small intestine and squamous-cell carcinomas and sebaceous gland carcinomas of the ear duct. In addition to these tumors, 4′-fluoro-4-acetylaminobiphenyl induced a high incidence of liver tumors in male rats at 10–12 months.

  3. 3-Hydroxy-4-aminobiphenyl and its N-acetyl derivative were noncarcinogenic. These compounds do not appear to be the effective carcinogen when 4-aminobiphenyl or its N-acetyl derivative is administered.

  4. The following compounds had little or no carcinogenic activity under our conditions: 2-methyl-, 2′-methyl-, 2′-fluoro-, and 3-amino-4-acetylaminobiphenyl; 3-amino-4-dimethylaminobiphenyl; 2- and 3-acetylaminobiphenyl; 4-fluorobiphenyl; 4-acetylamino-p-terphenyl; acetanilide; and 3,4-dimethylacetanilide.

  5. Rats fed N,N′-diacetylbenzidine developed a fatal glomerulonephritis which prevented adequate tests for carcinogenic activity. 2-Methyl-N,N′-diacetylbenzidine had moderate carcinogenic activity similar to that of 4-acetylaminobiphenyl; 3,3′-dimethyl-N,N′-diacetylbenzidine had weak activity; and 2,2′-dimethyl-N,N′-diacetylbenzidine was inactive.

  6. The syntheses of the following new compounds are described: 3-hydroxy-4-aminobiphenyl, 3-hydroxy-4-acetylaminobiphenyl, and 2′-fluoro-4-acetylaminobiphenyl.

*

This work was supported by grants-in-aid from the National Cancer Institute, United States Public Health Service (No. C355), and the Alberta Branch of the Canadian Cancer Society, and by an institutional grant from the Alexander and Margaret Stewart Trust Fund.

Some of these data have been presented in preliminary form (21, 25, 31).

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