Further studies on the carcinogenicity of dyes related to 4-dimethylaminoazobenzene; the requirement for an unsubstituted 2-position.

Our preceding report (24) dealt with the carcinogenicity of several polyfluoro derivatives of 4-dimethylaminoazobenzene (DAB) involving the equivalent positions of the prime ring (Chart 1). As in the case of the monofluoro derivatives (24, 26), all these compounds are more active carcino gens for the rat liver than the unsubstituted dye. These results are in great contrast to those ob tained after the substitution of other groups which are larger or more easily metabolized (22-24, 26). Hence, we have concluded that no position on the prime ring of DAB is directly concerned in the carcinogenic process induced by this dye. The pres ent report extends this approach to the other ring of the dye. The data indicate that an unsubstitut ed 2-position is necessary for carcinogenic activity and for the formation of protein-bound dye in the liver. This conclusion is in agreement with data (29, 30) indicating that the polar dyes released by alkaline hydrolysis of the protein-bound dye formed in vivo from 3'-methyl-DAB contain polar groups in the 2-position. The requirement of an unsubstituted 2-position for the carcinogenicity of DAB also implicated several other possible metabolites in the carcino genic process. Data are presented on the hepatocarcinogenicity of these and a variety of other derivatives of DAB.