alpha-Hydroxylation pathway in the in vitro metabolism of carcinogenic nitrosamines: N-nitrosodimethylamine and N-nitroso-N-methylaniline

Abstract

Evolution of 15N2-labeled molecular nitrogen was used to gauge the extent of alpha-hydroxylation during rat liver homogenate metabolism of doubly 15N-labeled N-nitrosodimethylamine (DMN) and N-nitrosomethylaniline (NMA). These measurements were correlated with the extent of total metabolism as measured by the disappearance of the nitrosamines and by the formation of formaldehyde. The results indicate that approximately 34% of DMN and 19% of NMA were metabolized by the alpha-hydroxylation pathway. Positive controls utilizing doubly 15N-labeled N-nitroso-N-methylurea yielded 96% of labeled nitrogen. These results are in variance with previously published data which claimed that either less than 5% or about 100% of DMN is metabolized by that route in vitro. Formaldehyde formation was shown to be a poor measure of the extent of metabolism. Semicarbazide gave rise to both formaldehyde and nitrogen, which makes it an undesirable component of the in vitro metabolism mixtures, particularly when those two substances are being measured.