RESUMEN
Myosmine is a minor tobacco alkaloid with widespread occurrence in the human diet. Myosmine is genotoxic in human cells and is readily nitrosated and peroxidated yielding reactive intermediates with carcinogenic potential. For biomonitoring of short-term and long-term exposure, analytical methods were established for determination of myosmine together with nicotine and cotinine in plasma, saliva and toenail by gas chromatography-mass spectrometry (GC/MS). Validation of the method with samples of 14 smokers and 10 non-smokers showed smoking-dependent differences of myosmine in toenails (66 +/- 56 vs 21 +/- 15 ng g(-1), p <0.01) as well as saliva (2.54 +/- 2.68 vs 0.73 +/- 0.65 ng ml(-1), p <0.01). However, these differences were much smaller than those with nicotine (1971 +/- 818 vs 132 +/- 82 ng g(-1), p <0.0001) and cotinine (1237 +/- 818 vs <35 ng g(-1)) in toenail and those of cotinine (97.43 +/- 84.54 vs 1.85 +/- 4.50 ng ml(-1), p <0.0001) in saliva. These results were confirmed in plasma samples from 84 patients undergoing gastro-oesophageal endoscopy. Differences between 25 smokers and 59 non-smokers are again much lower for myosmine (0.30 +/- 0.35 vs 0.16 +/- 0.18 ng ml(-1), p <0.05) than for cotinine (54.67 +/- 29.63 vs 0.61 +/- 1.82 ng ml(-1), p <0.0001). In conclusion, sources other than tobacco contribute considerably to the human body burden of myosmine.
Asunto(s)
Alcaloides/análisis , Cotinina/análisis , Cromatografía de Gases y Espectrometría de Masas/métodos , Uñas/química , Nicotina/análisis , Saliva/química , Alcaloides/química , Animales , Bovinos , Endoscopía Gastrointestinal , Esofagoscopía , Femenino , Humanos , Masculino , Estructura Molecular , Humo , Nicotiana/químicaRESUMEN
4-Hydroxy-1-(3-pyridyl)-1-butanone (HPB)-releasing DNA adducts are formed by metabolic activation of the tobacco-specific nitrosamines 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and N'-nitrosonornicotine (NNN). NNK and NNN are considered carcinogenic to humans by the International Agency for Research on Cancer. Existing analytical methods for determination of HPB-releasing DNA adducts require 0.3-2.0 g of human target tissues such as lung and esophagus. For adduct determination in milligram amounts of biopsy samples, an ultrasensitive and specific method is presented using capillary gas chromatography coupled to a high-resolution mass spectrometer operated in the negative chemical ionization mode (GC-NCI-HRMS). The method has a limit of detection of 4.6 fmol HPB, a limit of quantification of 14.9 fmol HBP and a recovery of 45 +/- 15%. Intra- and inter-day imprecision for N = 6 samples were calculated with coefficients of variation of <3.1%. Method applicability was evaluated with biopsies of esophageal mucosa (N = 14) yielding 5.6 +/- 1.9 mg tissue and a mean adduct level of 6.13 +/- 9.35 pmol HPB/mg DNA.