Assessment of no-observed-effect-levels for DNA adducts formation by genotoxic carcinogens in fetal turkey livers.

Autor: Kobets T; Department of Pathology, Microbiology and Immunology, New York Medical College, Valhalla, NY 10595, USA. Electronic address: Tetyana_Kobets@nymc.edu., Hickey C; Firmenich, Inc., Plainsboro, NJ 08536, USA., Johnson G; Swansea University Medical School, Swansea, Wales, UK., Duan JD; Department of Pathology, Microbiology and Immunology, New York Medical College, Valhalla, NY 10595, USA., Etter S; Firmenich SA, Geneva, Switzerland., Smith B; Monell Chemical Senses Center, Philadelphia, PA 19104, USA., Williams GM; Department of Pathology, Microbiology and Immunology, New York Medical College, Valhalla, NY 10595, USA.
Jazyk: angličtina
Zdroj: Toxicology [Toxicology] 2024 Jan; Vol. 501, pp. 153714. Date of Electronic Publication: 2023 Dec 22.
DOI: 10.1016/j.tox.2023.153714
Abstrakt: For genotoxic carcinogens, covalent binding to DNA is a critical initiating event in tumorigenesis. The present research investigated dose-effect relationships of three genotoxic carcinogens representing different structural classes, 2-acetylaminofluorene (2-AAF), benzo[a]pyrene (B[a]P) and quinoline (QUI), to assess the existence of no-observed-effect-levels (NOELs) for the formation of DNA adducts. Carcinogens were administered into the air sac of fertilized turkey eggs over wide dose ranges in three daily injections on days 22 to 24 of incubation. DNA adducts were measured in the fetal turkey livers by the 32 P-nucleotide postlabeling (NPL) assay. B[a]P and QUI produced DNA adducts in a dosage-related manner and exhibited NOELs at 0.65 and 0.35 mg/kg bw/day, respectively. In contrast, 2-AAF formed DNA adducts at all tested dosages down to 0.005 mg/kg bw/day. Benchmark dose (BMD) analysis identified the potencies of 2-AAF and QUI to be similar, while B[a]P was the least potent compound. Overall, findings in fetal turkey livers demonstrated that exposure levels to genotoxic compounds that do not result in DNA adducts can exist but are not evident with all carcinogens of this type. The use of mechanistic dose-effect studies for genotoxic endpoints can provide critical information for prioritization of concerns for risk assessment.
Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Tetyana Kobets reports financial support was provided by Firmenich Inc. Benjamin Smith reports financial support was provided by Singapore National Research Foundation Whitespace grant.
(Copyright © 2023 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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