title: Biological fate of styrene oxide adducts with globin: Elimination of cleavage products in the rat urine.
abstract: The in vivo fate of globin adducts with styrene 7,8-oxide (SO), an electrophilic metabolic intermediate of styrene, was studied in male Wistar rats dosed intraperitoneally with racemic SO, 100mg/kg b.w. Regioisomeric hydroxy(phenyl)ethyl (HPE) adducts at Cys, N-terminal Val, Lys and His in globin were determined and their elimination from blood was followed during 60days, corresponding to life span of rat erythrocytes. In the rat urine, Nα-acetylated products of hydrolytic cleavage of the HPE adducts with Cys, Lys and His were determined. On the first day post-exposure, abundant Nα-acetyl-HPE-Cys adducts (mercapturic acids) formed via direct conjugation of SO with hepatic glutathione were excreted rapidly, but then a much slower phase of elimination reflecting formation of Nα-acetyl-HPE-Cys via cleavage of the adducted globin was observed. A two-phase elimination occurred also in urinary Nα-acetyl-HPE adducts with His and Lys. While a decline by 75-85% during the first 7days post-exposure most likely reflected elimination of adducted albumin, the subsequent slow decline until day 60 corresponded to elimination kinetics of the adducted globin. Thus, the study not only provided original data on the fate of SO-globin adducts but also allowed to reveal general toxicokinetics properties of the urinary cleavage products as a novel type of chemical exposure biomarkers.
authors: Centre of Occupational Health, National Institute of Public Health, Šrobárova 48, 100 42 Prague, Czech Republic. Electronic address: jmraz@szu.cz.
authors: Jaroslav
authors: J
authors: Mráz
authors: Centre of Occupational Health, National Institute of Public Health, Šrobárova 48, 100 42 Prague, Czech Republic.
authors: Iveta
authors: I
authors: Hanzlíková
authors: Centre of Occupational Health, National Institute of Public Health, Šrobárova 48, 100 42 Prague, Czech Republic.
authors: Šárka
authors: Š
authors: Dušková
authors: Centre of Occupational Health, National Institute of Public Health, Šrobárova 48, 100 42 Prague, Czech Republic.
authors: Ludmila
authors: L
authors: Dabrowská
authors: Centre of Occupational Health, National Institute of Public Health, Šrobárova 48, 100 42 Prague, Czech Republic.
authors: Hana
authors: H
authors: Chrástecká
authors: Centre of Occupational Health, National Institute of Public Health, Šrobárova 48, 100 42 Prague, Czech Republic.
authors: Radka
authors: R
authors: Vajtrová
authors: Department of Organic Chemistry, Faculty of Chemical Technology, University of Chemistry and Technology, Technická 1905, 166 28 Prague, Czech Republic.
authors: Igor
authors: I
authors: Linhart
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism / Q000652:urine; D004784:Environmental Monitoring; D004785:Environmental Pollutants / Q000737:chemistry / Q000378:metabolism / Q000652:urine; D004852:Epoxy Compounds / Q000737:chemistry / Q000378:metabolism*; D005914:Globins / Q000378:metabolism* / Q000652:urine*; D006868:Hydrolysis; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D015262:Xenobiotics
chemical_list: D015415:Biomarkers; D004785:Environmental Pollutants; D004852:Epoxy Compounds; D015262:Xenobiotics; D005914:Globins; C013690:styrene oxide
keywords: Biological monitoring; Globin adducts; Hydroxy(phenyl)ethyl mercapturic acids; Styrene oxide; Urinary adducts