Benzo[a]pyrene and Caenorhabditis elegans: defining the genotoxic potential in an organism lacking the classical CYP1A1 pathway.


Journal

Archives of toxicology
ISSN: 1432-0738
Titre abrégé: Arch Toxicol
Pays: Germany
ID NLM: 0417615

Informations de publication

Date de publication:
03 2021
Historique:
received: 21 07 2020
accepted: 22 12 2020
pubmed: 10 1 2021
medline: 28 10 2021
entrez: 9 1 2021
Statut: ppublish

Résumé

Benzo[a]pyrene (BaP) is bioactivated in most organisms by the cytochrome P450 (CYP) enzymes, mainly CYP1A1, ultimately resulting in the reactive metabolite BaP-7,8-dihydrodiol-9,10-epoxide (BPDE) capable of covalently binding to DNA and forming adducts. This step has been defined as the key process in cancer initiation in humans. However, limited knowledge is available about the consequences of BaP exposure in organisms lacking this classical CYP1A1 pathway, one example is the model nematode Caenorhabditis elegans. The aim of this study was to define the genotoxic potential of BaP in C. elegans and to advance our understanding of xenobiotic processing in the absence of the CYP1A1 pathway. Exposure to high concentrations of BaP (0-40 µM) significantly affected life cycle endpoints of C. elegans, which were manifested by a reduced reproductive output and shortened life span. An optimised comet assay revealed that DNA damage increased in a dose-dependent manner; however, no bulky DNA adducts (dG-N

Identifiants

pubmed: 33420596
doi: 10.1007/s00204-020-02968-z
pii: 10.1007/s00204-020-02968-z
pmc: PMC7904753
doi:

Substances chimiques

CYP35 protein, C elegans 0
Caenorhabditis elegans Proteins 0
Mutagens 0
Benzo(a)pyrene 3417WMA06D
Cytochrome P-450 Enzyme System 9035-51-2
Cytochrome P-450 CYP1A1 EC 1.14.14.1

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1055-1069

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Auteurs

Mustafa Abbass (M)

Department of Analytical, Environmental and Forensic Sciences, School of Population Health and Environmental Sciences, Faculty of Life Sciences and Medicine, King's College London, London, UK.

Yuzhi Chen (Y)

Department of Analytical, Environmental and Forensic Sciences, School of Population Health and Environmental Sciences, Faculty of Life Sciences and Medicine, King's College London, London, UK.

Volker M Arlt (VM)

Department of Analytical, Environmental and Forensic Sciences, School of Population Health and Environmental Sciences, Faculty of Life Sciences and Medicine, King's College London, London, UK.
Toxicology Department, GAB Consulting GmbH, 69126, Heidelberg, Germany.

Stephen R Stürzenbaum (SR)

Department of Analytical, Environmental and Forensic Sciences, School of Population Health and Environmental Sciences, Faculty of Life Sciences and Medicine, King's College London, London, UK. stephen.sturzenbaum@kcl.ac.uk.

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Classifications MeSH