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The Metabolism of Methylated Aminoazo Dyes

III. The Demethylation of Various N-Methyl-C¹⁴-aminoazo Dyes in Vivo^*

( McArdle Memorial Laboratory, The Medical School, University of Wisconsin, Madison 6, Wis.)

1. The synthesis of the following N-methyl-C¹⁴-labeled dyes is described: 4-dimethylaminoazobenzene (DAB), 4-monomethylaminoazobenzene (MAB), and their 3-methyl and 4'-methyl derivatives.

2. Single doses of these labeled dyes (except 3-methyl-DAB) and N-methyl-C¹⁴-labeled 3'-methyl-DAB were administered by stomach tube to rats prefed a semi-purified diet or the same diet containing the corresponding unlabeled dye for 3 weeks. In all cases the administered radioactivity appeared rapidly in the expired CO₂. By 48 hours 50–70 per cent of the C¹⁴ had been expired as C¹⁴O₂, 10–30 per cent had been excreted in the urine, and 4–9 per cent had been excreted in the feces. The general metabolic pattern was the same, regardless of the dye used or whether the rats were fed a basal or dye-containing diet prior to the test dose.

3. In other experiments, protein, protein-bound serine, and choline were isolated from the livers of male rats given DAB, 3'-methyl-DAB, 4'-methyl-DAB, or 3-methyl-MAB; choline was also isolated from the livers of female rats given DAB. The specific activities of these liver components were essentially the same regardless of the dye fed or the sex of the rat. All the radioactivity in the serine was in the ß-position, and, on the average, approximately 80 per cent of the activity in the choline was in the N-methyl groups. These in vivo data and other in vitro data indicate that the methyl groups of each of the dyes are oxidized to formaldehyde via an intermediate such as the N-hydroxymethyl dye.

4. Thus, within the limitations of these methods, no differences in the metabolism of the methyl groups of strong and weak carcinogens or of N-dimethyl and N-monomethyl dyes could be detected.

^* This work was supported in part by grants from the National Cancer Institute of the National Institutes of Health, Public Health Service, the American Cancer Society, upon recommendation from the National Research Council, and the Alexander and Margaret Stewart Trust Fund.

Received 11/13/52.