Formation and metabolism of nitrosaminesin vivo, monitored by15N-stable isotope labelling

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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.