Formation and metabolism of nitrosamines in vivo, monitored by ¹⁵N-stable isotope labelling

Abstract

1. Microsomal metabolism of N-nitrosodimethylamine entails release of molecular nitrogen; the extent is determined by ¹⁵N stable isotope labelling and mass-spectrometric isotope ratio measurements.

2. Exhalation of labelled nitrogen by rats treated with ¹⁵N-dimethylamine and nitrite or ¹⁵N-nitrite alone indicates that nitrogen may arise from nitrite via two pathways: either directly from nitrosation of primary amines or from secondary and tertiary amines with subsequent enzymic N-demethylation.

3. The overall yield of nitrosamine formation, N-demethylation and nitrogen-release represent about 0.3–6% or the administered dose of dimethylamine (1.1 mmol/kg), depending upon the dose of nitrite (0.55–2.2 mmol/kg).

4. ¹⁵N-stable isotope labelling and mass-spectrometric isotope ratio measurements are powerful tools for assessment of endogenous nitrosamine formation from nitrite. One hundred nmol of labelled nitrogen are easily detectable in vivo; with further methodological refinement the limit of detection may be lowered by two orders of magnitude.