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Titolo:
Liquid chromatography electrospray-mass spectrometry of urinary aflatoxin biomarkers: Characterization and application to dosimetry and chemoprevention in rats
Autore:
Walton, M; Egner, P; Scholl, PF; Walker, J; Kensler, TW; Groopman, JD;
Indirizzi:
Johns Hopkins Sch Hyg & Publ Hlth, Dept Environm Hlth Sci, Baltimore, MD 21205 USA Johns Hopkins Sch Hyg & Publ Hlth Baltimore MD USA 21205 re, MD 21205 USA Johns Hopkins Univ, Appl Phys Lab, Laurel, MD 20733 USA Johns Hopkins Univ Laurel MD USA 20733 ppl Phys Lab, Laurel, MD 20733 USA
Titolo Testata:
CHEMICAL RESEARCH IN TOXICOLOGY
fascicolo: 7, volume: 14, anno: 2001,
pagine: 919 - 926
SICI:
0893-228X(200107)14:7<919:LCESOU>2.0.ZU;2-Z
Fonte:
ISI
Lingua:
ENG
Soggetto:
REPUBLIC-OF-CHINA; INDUCED HEPATIC TUMORIGENESIS; MOLECULAR DOSIMETRY; LIVER-CANCER; DNA ADDUCTS; AFFINITY-CHROMATOGRAPHY; ALBUMIN ADDUCTS; EXCRETION; OLTIPRAZ; CARCINOGENESIS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
39
Recensione:
Indirizzi per estratti:
Indirizzo: Groopman, JD Johns Hopkins Sch Hyg & Publ Hlth, Dept Environm Hlth Sci, 615 N Wolfe St,Baltimore, MD 21205 USA Johns Hopkins Sch Hyg & Publ Hlth 615 N Wolfe St Baltimore MD USA 21205
Citazione:
M. Walton et al., "Liquid chromatography electrospray-mass spectrometry of urinary aflatoxin biomarkers: Characterization and application to dosimetry and chemoprevention in rats", CHEM RES T, 14(7), 2001, pp. 919-926

Abstract

A liquid chromatography electrospray tandem mass spectrometry (LC-ESI-MS/MS) method for the measurement of aflatoxin biomarkers in urine has been developed and validated. The two major aflatoxin-DNA adducts formed in rat tissues, aflatoxin N-7-guanine and its imidazole ring opened derivative, 8,9-dihydro-8-(2,6-diamino-4-oxo-3,4-dihydropyrimid-5-yl formamido)-9-hydroxy-aflatoxin B-1, were detected and quantified in urine by the LC-ESI-MS/MS technique. Other metabolites derived from the conjugation and/or oxidation of aflatoxin B1 measured in the urine of dosed rats included aflatoxin Fl, aflatoxin P-1-glucuronide, aflatoxin Q(1), aflatoxin M-1, 8,9-dihydro-8,9-dihydroxy aflatoxin B-1, aflatoxin B-1-mercapturic acid, the aflatoxin-cysteine glycine adduct derived from the aflatoxin-glutathione conjugate, aflatoxin M1P1 and the aflatoxin B-1-dialcohol. For in vivo studies to determine the dosimetry of certain aflatoxin metabolites, aflatoxin Ba was used as an internal standard for recovery since this compound is not naturally produced in rats. In the final method using the internal standard, the coefficient ofvariation of six replicate analyses of in vivo rat urine samples for aflatoxin N-7-guanine, aflatoxin B-1-mercapturic acid, and aflatoxin M-1 was 12.5, 12.8, and 5.8%, respectively. Further, the LC-ESI-MS/MS method to detectaflatoxin N-7-guanine in in vivo rat urine samples was at least 20-fold more sensitive than prior techniques. Using the LC-ESI-MS/MS technique, the dosimetry, on a weekly basis, of major urinary aflatoxin metabolites was assessed in animals chronically dosed over a 5-week period. Of particular importance was the application of this method to determine the modulation of levels of urinary aflatoxin metabolites by treatment with oltipraz, a chemopreventive agent that can completely ablate aflatoxin hepatocarcinogenesis inthe rat. After 1 week, oltipraz administration diminished urinary aflatoxin N-7-guanine, aflatoxin B-1-mercapturic acid and aflatoxin M-1 levels by 83, 92, and 82%, respectively. The magnitude of this reduction was persistent at the day 14, 21, 28, and 35-day time points with the average decrease of aflatoxin N-7-guanine, aflatoxin B-1-mercapturic acid and aflatoxin M-1 being 73, 92, and 90%, respectively. Importantly, even under circumstances where the oltipraz intervention was most efficient in reducing aflatoxin metabolite levels, the LC-ESI-MS/MS method was still sensitive enough to detect the reduced biomarker content, This outcome has important translational implications for the application and analysis of the efficacy of primary andsecondary prevention interventions in human populations where ambient exposure levels are low, but the toxicologic hazards of these exposures remain high.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 18/09/20 alle ore 17:06:07