Formation and metabolism of nitrosamines in vivo, monitored by 14N-stable isotope labelling.
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. 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. 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). 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.
D000818:Animals; D008297:Male; D013058:Mass Spectrometry; D008862:Microsomes, Liver / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D009587:Nitrogen Isotopes; D009602:Nitrosamines / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D009573:Nitrites; D009587:Nitrogen Isotopes; D009602:Nitrosamines