Novel aminoarylcysteine adducts in globin of rats dosed with naphthylamine and nitronaphthalene isomers
| Autor: | Hana Vachová, Monika Tvrdíková, Šárka Dušková, Jaroslav Mráz, Iveta Hanzlíková, Igor Linhart |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male Stereochemistry Health Toxicology and Mutagenesis 010501 environmental sciences Naphthalenes Toxicology 01 natural sciences Adduct 03 medical and health sciences chemistry.chemical_compound Naphthylamine Biotransformation 2-Naphthylamine Animals Globin Cysteine Rats Wistar Carcinogen 0105 earth and related environmental sciences General Medicine Glutathione Acetylcysteine Globins 030104 developmental biology 1-Naphthylamine chemistry Electrophile Biomarkers Injections Intraperitoneal Protein Binding |
| Zdroj: | Archives of toxicology. 95(1) |
| ISSN: | 1432-0738 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink