Novel aminonaphthylcysteine (ANC) adducts, formed via naphthylnitrenium ions and/or their metabolic precursors in the biotransformation of naphthylamines (NA) and nitronaphthalenes (NN), were identified and quantified in globin of rats dosed intraperitoneally with 0.16 mmol/kg b.w. of 1-NA, 1-NN, 2-NA and 2-NN. Using HPLC-ESI-MS2 analysis of the globin hydrolysates, S-(1-amino-2-naphthyl)cysteine (1A2NC) together with S-(4-amino-1-naphthyl)cysteine (4A1NC) were found in rats given 1-NA or 1-NN, and S-(2-amino-1-naphthyl)cysteine (2A1NC) in those given 2-NA or 2-NN. The highest level of ANC was produced by the most mutagenic and carcinogenic isomer 2-NA (35.8 ± 5.4 nmol/g globin). The ratio of ANC adduct levels for 1-NA, 1-NN, 2-NA and 2-NN was 1:2:100:3, respectively. Notably, the ratio of 1A2NC:4A1NC in globin of rats dosed with 1-NA and 1-NN differed significantly (2:98 versus 16:84 respectively), indicating differences in mechanism of the adduct formation. Moreover, aminonaphthylmercapturic acids, formed via conjugation of naphthylnitrenium ions and/or their metabolic precursors with glutathione, were identified in the rat urine. Their amounts excreted after dosing rats with 1-NA, 1-NN, 2-NA and 2-NN were in the ratio 1:100:40:2, respectively. For all four compounds tested, haemoglobin binding index for ANC was several-fold higher than that for the sulphinamide adducts, generated via nitrosoarene metabolites. Due to involvement of electrophilic intermediates in their formation, ANC adducts in globin may become toxicologically more relevant biomarkers of cumulative exposure to carcinogenic or non-carcinogenic arylamines and nitroarenes than the currently used sulphinamide adducts.

• Klíčová slova
• Arylamines, Arylnitrenium ions, Biomarker, Carcinogens, Globin adducts, Nitroarenes,
• MeSH
• 1-naftylamin aplikace a dávkování   metabolismus   toxicita   MeSH
• 2-naftylamin aplikace a dávkování   metabolismus   toxicita   MeSH
• acetylcystein analogy a deriváty   moč   MeSH
• biologické markery krev   moč   MeSH
• cystein MeSH
• globiny metabolismus   MeSH
• injekce intraperitoneální MeSH
• krysa rodu Rattus MeSH
• naftaleny aplikace a dávkování   krev   toxicita   MeSH
• potkani Wistar MeSH
• vazba proteinů MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• 1-naftylamin MeSH
• 1-nitronaphthalene MeSH Prohlížeč
• 2-naftylamin MeSH
• 2-nitronaphthalene MeSH Prohlížeč
• acetylcystein MeSH
• biologické markery MeSH
• cystein MeSH
• globiny MeSH
• naftaleny MeSH