کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2601330 | 1562652 | 2006 | 8 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: N-Methylcarbamoyl-lysine adduct in globin: A new metabolic product and potential biomarker of N,N-dimethylformamide in humans N-Methylcarbamoyl-lysine adduct in globin: A new metabolic product and potential biomarker of N,N-dimethylformamide in humans](/preview/png/2601330.png)
Metabolism of the solvents N,N-dimethylformamide (DMF) and N-methylformamide (MF) results in the formation of N-methylcarbamoyl adducts at the N-terminal valine and lysine in blood protein globin, of which the lysine adduct has so far only been reported in rats given high doses of both solvents [Mráz, J., Šimek, P., Chvalová, D., Nohová, H., Šmigolová, P., 2004. Studies on the methyl isocyanate adducts in globin. Chem. Biol. Interact. 148, 1–10]. Here we examined whether the lysine adduct is produced, and accessible to analysis, in humans occupationally or experimentally exposed to DMF. Globin from exposed subjects (n = 35) and unexposed controls (n = 5) was analyzed by two methods. Edman degradation was used as a sensitive reference method to measure the valine adduct by converting it to 3-methyl-5-isopropylhydantoin (MVH). The MVH levels in globin of the exposed subjects were in the range of 1–441 nmol/g, in controls <1 nmol/g. The principal method of globin analysis consisted of enzymatic hydrolysis with pronase to release free Nɛ-(N-methylcarbamoyl)lysine (MLU) and N-methylcarbamoylvaline (MVU), which were determined by HPLC/MS/MS, with no clean-up or preconcentration steps needed. For MLU, the parent and product ions were m/z 204 → 173, and the limit of detection was ∼5 nmol/g globin. MLU was found in most globins from the exposed subjects but not in the controls. A close correlation between the MLU and MVH levels (nmol/g) was observed: MLU = 7 + 0.48 MVH (R2 = 0.84, n = 32). In conclusion, MLU can be easily measured in globin of workers exposed to DMF. The findings also indicate a long-term persistence of MLU in the human body, and consequently, its potential as a biomarker of chronic exposure to DMF.
Journal: Toxicology Letters - Volume 162, Issues 2–3, 10 April 2006, Pages 211–218