CYTOCHROMES P450 2B1 AND P450 2B2 DEMETHYLATE N-NITROSODIMETHYLAMINE AND N-NITROSOMETHYLANILINE IN-VITRO

The demethylation of carcinogenic N-nitrosodimethylamine (NDMA) and N- nitrosomethylaniline (NMA) is catalyzed by purified rat liver cytochro mes P450 2B1 and 2B2 reconstituted with NADPH-P450 reductase and dilau roylphosphatidylcholine. A molar P450 to reductase ratio of about 1.0 is the most appropriate for the catalysis. NMA is a better substrate f or both P450 enzymes than NDMA, with K-m values of 0.34 and 0.43 mmol/ l for P450 2B1 and P450 2B2, respectively. For NDMA as the substrate, the K-m values were approx. ten times higher than those for NMA. With each isoenzyme only one K-m for NDMA or NMA was observed, whereas with liver microsomes of PB-pretreated rats, multiple K-m values were obta ined. The results strongly suggest that both P450 isoenzymes can be in volved in the metabolism of nitrosamines.