Staff Publications

Staff Publications

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    'Staff publications' is the digital repository of Wageningen University & Research

    'Staff publications' contains references to publications authored by Wageningen University staff from 1976 onward.

    Publications authored by the staff of the Research Institutes are available from 1995 onwards.

    Full text documents are added when available. The database is updated daily and currently holds about 240,000 items, of which 72,000 in open access.

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Record number 551636
Title Determination of genotoxic potencies of pyrrolizidine alkaloids in HepaRG cells using the γH2AX assay
Author(s) Louisse, Jochem; Rijkers, Deborah; Stoopen, Geert; Holleboom, Wendy Jansen; Delagrange, Mona; Molthof, Elise; Mulder, Patrick P.J.; Hoogenboom, Ron L.A.P.; Audebert, Marc; Peijnenburg, Ad A.C.M.
Source Food and Chemical Toxicology 131 (2019). - ISSN 0278-6915
DOI https://doi.org/10.1016/j.fct.2019.05.040
Department(s) BU Toxicology, Novel Foods & Agrochains
BU Contaminants & Toxins
VLAG
Publication type Refereed Article in a scientific journal
Publication year 2019
Keyword(s) Genotoxicity - HepaRG - Pyrrolizidine alkaloids (PAs) - Relative potency factor (RPF) - γH2AX assay
Abstract

Pyrrolizidine alkaloids (PAs) are secondary metabolites from plants that have been found in substantial amounts in herbal supplements, infusions and teas. Several PAs cause cancer in animal bioassays, mediated via a genotoxic mode of action, but for the majority of the PAs, carcinogenicity data are lacking. It is assumed in the risk assessment that all PAs have the same potency as riddelliine, which is considered to be one of the most potent carcinogenic PAs in rats. This may overestimate the risks, since many PAs are expected to have lower potencies. In this study we determined the concentration-dependent genotoxicity of 37 PAs representing different chemical classes using the γH2AX in cell western assay in HepaRG human liver cells. Based on these in vitro data, PAs were grouped into different potency classes. The group with the highest potency consists particularly of open diester PAs and cyclic diester PAs (including riddelliine). The group of the least potent or non-active PAs includes the monoester PAs, non-esterified necine bases, PA N-oxides, and the unsaturated PA trachelanthamine. This study reveals differences in in vitro genotoxic potencies of PAs, supporting that the assumption that all PAs have a similar potency as riddelliine is rather conservative.

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