This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Miller, J. A. Articles by Miller, E. C. Search for Related Content PubMed PubMed Citation Articles by Miller, J. A. Articles by Miller, E. C.

The Carcinogenic Activities of Certain Halogen Derivatives of 4-Dimethylaminoazobenzene in the Rat^*

(From the McArdle Memorial Laboratory, Medical School, University of Wisconsin, Madison 6, Wisconsin)

1. The carcinogenic activities of 15 halogen and other derivatives of the hepatic carcinogen, 4-dimethylaminoazobenzene, were determined in the rat. Some of these compounds were fed to test the hypothesis (Elson and associates) that the parent dye undergoes a benzidine rearrangement in vivo which is concerned in the carcinogenic process induced by the dye.

2. The substitution of the stable o, p-directing fluoro group in the 3' or 4' positions yielded dyes which were nearly twice as active as 4-dimethyl-aminoazobenzene, whereas the 2'-fluoro derivative had essentially the same activity as the parent dye. The activity of the 4'-fluoro derivative was strongly inhibited by high levels of dietary riboflavin, and the level of protein-bound dye formed in the liver from this dye reached a maximum after 1 month of feeding.

3. The substitution of the stable m-directing trifluoromethyl group in the 2', 3', or 4' positions yielded dyes that were inactive even after 8 months of continued administration.

4. Two dyes that presumably could not undergo the benzidine rearrangement in vivo, 2', 4', 6'-tribromo- and 2', 4', 6'-trichloro-4-dimethylaminoazo-benzene, were inactive, but the tribromo derivative was only poorly absorbed from the intestinal tract. However, the benzidine rearrangement product of 4-dimethylaminoazobenzene, 2, 4'-diamino-5-dimethylaminobiphenyl, was inactive even when fed at a high level for 10 months. In addition, the high activities of the 2'- and 4'-fluoro derivatives are considered to constitute positive evidence against the benzidine rearrangement hypothesis.

5. Two possible metabolites of 4-dimethylaminoazobenzene were tested: 4-formylmonomethyl-aminoazobenzene had only a low carcinogenic activity and 2-hydroxy-4-dimethylaminoazobenzene was inactive. The following miscellaneous derivatives were inactive under the conditions used: 2', 3-dimethyl-4-aminoazobenzene ("o-aminoazotoluene"), 2', 3-dimethyl-4-monomethylaminoazobenzene, and 4'-nitro-4-dimethylaminoazobenzene.

6. The following new compounds are described: 2'-fluoro-, 3'-fluoro-, 4'-fluoro-, 2'-trifluoromethyl-, 3'-trifluoromethyl-, 4'-trifluoromethyl-, 2', 4', 6-' trichloro-, and 2', 5'-dichloro-4-dimethylaminoazobenzene; 2', 3-dimethyl-4-monomethylamino-azobenzeneand 4-formylmonomethylaminoazobenzene.