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Tytuł pozycji:

DNA as an in vitro trapping agent for detection of bulky genotoxic metabolites.

Tytuł:
DNA as an in vitro trapping agent for detection of bulky genotoxic metabolites.
Autorzy:
Motwani HV; Department of Environmental Science, Stockholm University, SE-106 91 Stockholm, Sweden. Electronic address: .
Źródło:
Journal of chromatography. B, Analytical technologies in the biomedical and life sciences [J Chromatogr B Analyt Technol Biomed Life Sci] 2020 Sep 01; Vol. 1152, pp. 122276. Date of Electronic Publication: 2020 Jul 18.
Typ publikacji:
Journal Article
Język:
English
Imprint Name(s):
Original Publication: Amsterdam ; New York : Elsevier, c2002-
MeSH Terms:
DNA Adducts*/analysis
DNA Adducts*/chemistry
DNA Adducts*/metabolism
Mutagens*/analysis
Mutagens*/chemistry
Mutagens*/metabolism
DNA/*metabolism
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide/analysis ; 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide/chemistry ; 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide/metabolism ; Animals ; Benzo(a)pyrene/analysis ; Benzo(a)pyrene/chemistry ; Benzo(a)pyrene/metabolism ; Chromatography, Liquid/methods ; Linear Models ; Mass Spectrometry/methods ; Microsomes, Liver/metabolism ; Models, Chemical ; Rats ; Reproducibility of Results ; Sensitivity and Specificity
Contributed Indexing:
Keywords: DNA; Genotoxic metabolites; High resolution mass spectrometry; In vitro metabolism; Polycyclic aromatic hydrocarbons
Substance Nomenclature:
0 (DNA Adducts)
0 (Mutagens)
3417WMA06D (Benzo(a)pyrene)
55097-80-8 (7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide)
9007-49-2 (DNA)
Entry Date(s):
Date Created: 20200730 Date Completed: 20210412 Latest Revision: 20210412
Update Code:
20240104
DOI:
10.1016/j.jchromb.2020.122276
PMID:
32721860
Czasopismo naukowe
The instability of electrophilic reactive metabolites in in vitro metabolism studies makes their accurate analysis challenging. To stabilise the reactive compounds prior to their analysis, different trapping agents, such as thiols, amines and cob(I)alamin, have earlier been tested depending on the metabolites to be analysed and the type of study. In the present work, DNA is introduced as a trapping agent for measuring the formation of bulky electrophilic metabolites. Benzo[a]pyrene (B[a]P), a polycyclic aromatic hydrocarbon (PAH), was used as a model compound in a rat liver S9 metabolic system. Under physiological incubation conditions, B[a]P metabolises to diol epoxide (BPDE) metabolites which were trapped by DNA resulting in the formation of covalently bound DNA adducts. The methodology for analysis of these adducts included extraction of the DNA from the metabolic system, digestion of the DNA to yield nucleosides and analysis of the BPDE-adduct to deoxyguanosine (BPDE-dG) by liquid chromatography coupled to high resolution mass spectrometry (HRMS). The chromatographic conditions in combination with the high mass accuracy data (±3 ppm) was useful in resolving BPDE-dG in its protonated form from the complex set of ions present in the metabolic matrix. The method was validated in terms of sensitivity, specificity, accuracy, precision and recovery, and applied to provide a preliminary estimate of BPDE-dG levels from the metabolism of B[a]P in rat S9. The use of DNA as a trapping agent for in vitro metabolites has a potential to aid in cancer risk assessment procedure of PAHs, for instance, in inter-species comparison of metabolism to reactive metabolites and can be adapted for screening of genotoxic metabolites, e.g., from emerging environmental contaminants.
Competing Interests: Declaration of Competing Interest The author declares that he has no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2020 The Author. Published by Elsevier B.V. All rights reserved.)

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