AN INVESTIGATION OF THE METABOLISM OF N-NITROSODIMETHYLAMINE AND N-NITROSOMETHYLANILINE BY HORSERADISH-PEROXIDASE IN-VITRO

The demethylation of carcinogenic N-nitrosodimethylamine (NDMA) and N- nitrosomethylaniline (NMA) is catalyzed by horseradish peroxidase in t he presence of hydrogen peroxide. NMA is a better substrate for peroxi dase than NDMA. The K-m values are 0.74 and 3.12 mmol/l for NMA and ND MA, respectively. The oxidation of NDMA and NMA is inhibited by radica l trapping agents (nitrosobenzene, glutathione, ascorbate, NADH). This indicates the radical mechanism for the peroxidase-mediated oxidation of both N-nitrosamines. The in vitro metabolism of NMA using peroxida se was investigated in detail. Beside formaldehyde, the metabolites fo rmed from NMA by peroxidase include aniline, p-aminophenol and phenol. Phenol formation presumably arose from N-demethylation of NMA via a b enzenediazonium ion (BDI) intermediate while aniline and p-aminophenol from denitrosation of this carcinogen. The results are discussed from the point of view of the role of peroxidases in the metabolism of N-n itrosamines.