N-Methylcarbamoyl-lysine adduct in globin: a new metabolic product and potential biomarker of N,N-dimethylformamide in humans

0047087 - BC 2007 RIV IE eng J - Journal Article
Mráz, J. - Cimlová, Jana - Stránský, V. - Nohová, H. - Kičová, R. - Šimek, Petr
N-Methylcarbamoyl-lysine adduct in globin: a new metabolic product and potential biomarker of N,N-dimethylformamide in humans.
[Adukt N-Methylkarbamoyl-lysinu v hemoglobinu: nový metabolický produkt a potenciální biomarker expozice N,N-dimethylformamidu u člověka.]
Toxicology Letters. Roč. 162, 2-3 (2006), s. 211-218. ISSN 0378-4274. E-ISSN 1879-3169
R&D Projects: GA ČR(CZ) GA303/00/0923
Institutional research plan: CEZ:AV0Z50070508
Keywords : N,N-dimethylformamide * globin * adducts
Subject RIV: CE - Biochemistry
Impact factor: 2.784, year: 2006

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. Globin from exposed subjects to DMF (n = 35) and unexposed controls (n = 5) was analyzed by 2 methods. Edman degradation was used as 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 involved enzymatic hydrolysis with pronase to release free N-epsilon-(N-methylcarbamoyl)lysine (MLU) and N-methyl-carbamoylvaline (MVU), which were directly determined by HPLC/MS/MS. 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 (R-2 = 0.84, n = 32).

Metabolismus rozpouštědel N,N-dimethylformamidu (DMF) a N-methylformamidu (MF) vede ke vzniku N-methylkarbamoylových aduktů s krevním globinem na N-terminálovém valinu a lysinu. Globin osob vystavených DMF (n = 35 ) a kontroly (n = 5) byly analyzovány dvěma metodami. Edmanova degradace byla použita k měření valinového aduktu 3-methyl-5-isopropylhydantoinu (MVH). MVH hladiny u exponovaných osob byly v rozmezí 1-441 nmol/g, v kontrolách < 1 nmol/g. Hlavní použitá metoda zahrnovala enzymatickou pronázovou hydrolýzu a následnou HPLC/M/MS analýzu N-epsilon-(N-methylkarbamoyl)lysinu (MLU) and N-methyl-karbamoylvaline (MVU). MLU byl nalezen ve většině globinů u exponovaných subjektů, ale ne v kontrolách. Byla pozorována blízká korelace mezi hladinami MLU a MVH (nmol/g) : MLU = 7 + 0.48 MVH (R-2 = 0.84, n = 32). Poznatky naznačují dlouhodobou persitenci MLU v lidském těle, a tak jeho potenciál posloužit jako biomarker chronické expozice DMF.
Permanent Link: http://hdl.handle.net/11104/0138099