3-nitro-o-phenylenediamine and 4-phenylenediamine

Topics: Aniline Compounds; Nitro Compounds; Oxidation-Reduction; Phenylenediamines; Radiation Effects; Research

Topics: Biphenyl Compounds; Coloring Agents; Nitro Compounds; Oxidation-Reduction; Phenylenediamines; Tocopherols; Vitamin E Deficiency

Topics: Animals; Biphenyl Compounds; Coloring Agents; Nitro Compounds; Phenylenediamines; Rats

1. Eighteen known or possible metabolites of the hepatic carcinogen 4- (or p-) dimethylaminoazobenzene were tested for carcinogenic activity in the rat. Of these compounds only 4-monomethylaminoazobenzene, a known metabolite, proved to be active. Eight compounds, which appear to be metabolites of the dye, were inactive; these included 4-aminoazobenzene, 4'-hydroxy-4-monomethylaminoazobenzene, 4'-hydroxy-4-aminoazobenzene, N-methyl-p-phenylenediamine, p-phenylenediamine, aniline, p-aminophenol, and o-aminophenol. Nine compounds which may possibly be metabolites also were inactive; these compounds were 4'-hydroxy-, 3'-hydroxy-, and 2'-hydroxy-4-dimethylaminoazobenzene, 4-formylaminoazobenzene, 4-hydroxyazobenzene, 2, 4'-diamino-5-dimethylaminodiphenyl, 3-dimethylaminocarbazole, N,N-dimethyl-p-phenylenediamine, and p-hydroquinone. A mixture of 9 known and possible metabolites was also found to be inactive. These data indicate that the primary carcinogen operative in tumor formation by 4-dimethylaminoazobenzene is probably an azo dye closely related to the parent carcinogen. This conclusion is supported by recent work from this laboratory which indicates that the primary carcinogen consists of either or both of the protein-bound dyes found in the liver, i.e. 4-monomethylaminoazobenzene and an unidentified polar aminoazo dye, and that the formation of bound dye constitutes one of the first steps in this carcinogenic process. 2. The carcinogenic activities of 19 other compounds related to 4-dimethyl-aminoazobenzene were tested to obtain more information on the structural features needed for a 4-aminoazo dye to possess strong activity in the rat. 3'-Methyl-4-monomethylaminoazobenzene and the corresponding dimethylamino derivative were nearly twice as active and 4-ethylmethylaminoazobenzene had the same activity as 4-dimethylaminoazobenzene. As tested 3'-nitro- and 3'-chloro-4-dimethylaminoazobenzene both had about the same activity as 4-dimethylaminoazobenzene; however, since the 3'-nitro derivative was incompletely absorbed its real activity appears to be about 1(1/2) times that of 4-dimethylaminoazobenzene. 2'-Nitro- and 2'-chloro-4-dimethylaminoazobenzene were about one-half to one-third as active and 4'-chloro-4-dimethylaminoazobenzene was approximately one-fourth as active as the parent dye. 3'-Ethoxy-4-dimethylaminoazobenzene and 3-methyl-4-monomethylaminoazobenzene exhibited only slight carcinogenic activity. The following compounds proved inactive: the b

Topics: Aminophenols; Animals; Azo Compounds; Carcinogens; Nitro Compounds; p-Aminoazobenzene; p-Dimethylaminoazobenzene; Phenylenediamines; Rats