A correlation of the rate of N-hydroxylation of aminoazo dyes with their carcinogenic activity in the rat.

The rate of formation of N-hydroxy-N-methyl-4-aminoazobenzene (N-OH-MAB) derivatives from N,N-dimethyl-4-aminoazobenzene (DAB) derivatives and from N-methyl-4-aminoazobenzene (MAB) derivatives was measured by the e.s.r. spectroscopy, and the rate of N-demethylation of DAB derivatives was measured by h.p.l.c. The rate of formation of N-OH-MAB derivatives from DAB derivatives showed a strong correlation with their carcinogenic activity. This reaction occurs in two-steps, i.e. N-demethylation followed by N-hydroxylation. The rate of N-demethylation of DAB derivatives was not correlated with their carcinogenic activity. On the other hand, the rate of N-hydroxylation of MAB derivatives was well correlated with the carcinogenic activity of corresponding DAB derivatives. These results suggest that the carcinogenic activity of DAB derivatives in the rat was dependent upon the enzyme concerned with N-hydroxylation. The positive carcinogenicity is limited to those derivatives with a rate of N-hydroxylation above the threshold value.