Exposure of the Human HepaRG Liver Cell Line to Pyrrolizidine Alkaloids Results in a Gene Expression Profile Characteristic for Genotoxic Carcinogens

Research output: Contribution to conferenceAbstractAcademic

Abstract

Pyrrolizidine alkaloids (PAs) are secondary metabolites found in many
plant species and can be present as contaminants in food, herbal teas,
plant food supplements, and animal feed. A large number of PAs are toxic
not only to livestock and wildlife but also to humans. Hepatotoxicity,
genotoxicity, and carcinogenicity are the main toxicities observed in
experimental animals treated with PAs. However, there is little direct
evidence for mutagenicity and carcinogenicity of PAs in humans and epidemiological data are lacking. The present study aimed to contribute to
a better evaluation of the genotoxic and carcinogenic risks of PAs for humans.
To that end, the human hepatoma cell line HepaRG was exposed
in vitro for 72 hours to six PAs (riddelliine, retrorsine, echimidine, monocrotaline, lasiocarpine, senkirkine), and the genotoxic carcinogen benzo[
a]pyrene, the non-genotoxic carcinogen bis(2-ethylhexyl) phthalate,
and the non-carcinogen mannitol as controls. Upon exposure, RNA was
isolated and effects on whole genome mRNA expression were analysed
using DNA microarrays. Pathway analysis showed that several processes
involved in genotoxicity, including DNA damage response, p53 pathway
and cell cycle checkpoints, were modulated by the PAs. Comparison of
the array data with transcriptome data obtained by others upon exposure
of HepaRG to various model hepatocarcinogens showed that each
of the PAs used in the present study generated a gene expression profile
that is characteristic for genotoxic carcinogens.
Original languageEnglish
Pages1480
Number of pages1
Publication statusPublished - 29 Feb 2016
Event55th Annual Meeting SOT and ToxExpo - New Orleans, United States
Duration: 13 Mar 201617 Mar 2016
http://www.toxicology.org/events/am/AM2016/index.asp

Conference

Conference55th Annual Meeting SOT and ToxExpo
Abbreviated titleSOT 2016
CountryUnited States
CityNew Orleans
Period13/03/1617/03/16
Internet address

Fingerprint

pyrrolizidine alkaloids
carcinogens
hepatocytes
cell lines
gene expression
carcinogenicity
genotoxicity
riddelliine
retrorsine
monocrotaline
herbal tea
phthalates
hepatotoxicity
mutagenicity
food contamination
food animals
hepatoma
mannitol
transcriptome
DNA damage

Cite this

@conference{bbd47e87b51d4db7bababc757e830b0a,
title = "Exposure of the Human HepaRG Liver Cell Line to Pyrrolizidine Alkaloids Results in a Gene Expression Profile Characteristic for Genotoxic Carcinogens",
abstract = "Pyrrolizidine alkaloids (PAs) are secondary metabolites found in manyplant species and can be present as contaminants in food, herbal teas,plant food supplements, and animal feed. A large number of PAs are toxicnot only to livestock and wildlife but also to humans. Hepatotoxicity,genotoxicity, and carcinogenicity are the main toxicities observed inexperimental animals treated with PAs. However, there is little directevidence for mutagenicity and carcinogenicity of PAs in humans and epidemiological data are lacking. The present study aimed to contribute toa better evaluation of the genotoxic and carcinogenic risks of PAs for humans.To that end, the human hepatoma cell line HepaRG was exposedin vitro for 72 hours to six PAs (riddelliine, retrorsine, echimidine, monocrotaline, lasiocarpine, senkirkine), and the genotoxic carcinogen benzo[a]pyrene, the non-genotoxic carcinogen bis(2-ethylhexyl) phthalate,and the non-carcinogen mannitol as controls. Upon exposure, RNA wasisolated and effects on whole genome mRNA expression were analysedusing DNA microarrays. Pathway analysis showed that several processesinvolved in genotoxicity, including DNA damage response, p53 pathwayand cell cycle checkpoints, were modulated by the PAs. Comparison ofthe array data with transcriptome data obtained by others upon exposureof HepaRG to various model hepatocarcinogens showed that eachof the PAs used in the present study generated a gene expression profilethat is characteristic for genotoxic carcinogens.",
author = "A.A.C.M. Peijnenburg and G.M. Stoopen and T.H.G. Polman and P.J.M. Hendriksen",
year = "2016",
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language = "English",
pages = "1480",
note = "55th Annual Meeting SOT and ToxExpo, SOT 2016 ; Conference date: 13-03-2016 Through 17-03-2016",
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Exposure of the Human HepaRG Liver Cell Line to Pyrrolizidine Alkaloids Results in a Gene Expression Profile Characteristic for Genotoxic Carcinogens. / Peijnenburg, A.A.C.M.; Stoopen, G.M.; Polman, T.H.G.; Hendriksen, P.J.M.

2016. 1480 Abstract from 55th Annual Meeting SOT and ToxExpo, New Orleans, United States.

Research output: Contribution to conferenceAbstractAcademic

TY - CONF

T1 - Exposure of the Human HepaRG Liver Cell Line to Pyrrolizidine Alkaloids Results in a Gene Expression Profile Characteristic for Genotoxic Carcinogens

AU - Peijnenburg, A.A.C.M.

AU - Stoopen, G.M.

AU - Polman, T.H.G.

AU - Hendriksen, P.J.M.

PY - 2016/2/29

Y1 - 2016/2/29

N2 - Pyrrolizidine alkaloids (PAs) are secondary metabolites found in manyplant species and can be present as contaminants in food, herbal teas,plant food supplements, and animal feed. A large number of PAs are toxicnot only to livestock and wildlife but also to humans. Hepatotoxicity,genotoxicity, and carcinogenicity are the main toxicities observed inexperimental animals treated with PAs. However, there is little directevidence for mutagenicity and carcinogenicity of PAs in humans and epidemiological data are lacking. The present study aimed to contribute toa better evaluation of the genotoxic and carcinogenic risks of PAs for humans.To that end, the human hepatoma cell line HepaRG was exposedin vitro for 72 hours to six PAs (riddelliine, retrorsine, echimidine, monocrotaline, lasiocarpine, senkirkine), and the genotoxic carcinogen benzo[a]pyrene, the non-genotoxic carcinogen bis(2-ethylhexyl) phthalate,and the non-carcinogen mannitol as controls. Upon exposure, RNA wasisolated and effects on whole genome mRNA expression were analysedusing DNA microarrays. Pathway analysis showed that several processesinvolved in genotoxicity, including DNA damage response, p53 pathwayand cell cycle checkpoints, were modulated by the PAs. Comparison ofthe array data with transcriptome data obtained by others upon exposureof HepaRG to various model hepatocarcinogens showed that eachof the PAs used in the present study generated a gene expression profilethat is characteristic for genotoxic carcinogens.

AB - Pyrrolizidine alkaloids (PAs) are secondary metabolites found in manyplant species and can be present as contaminants in food, herbal teas,plant food supplements, and animal feed. A large number of PAs are toxicnot only to livestock and wildlife but also to humans. Hepatotoxicity,genotoxicity, and carcinogenicity are the main toxicities observed inexperimental animals treated with PAs. However, there is little directevidence for mutagenicity and carcinogenicity of PAs in humans and epidemiological data are lacking. The present study aimed to contribute toa better evaluation of the genotoxic and carcinogenic risks of PAs for humans.To that end, the human hepatoma cell line HepaRG was exposedin vitro for 72 hours to six PAs (riddelliine, retrorsine, echimidine, monocrotaline, lasiocarpine, senkirkine), and the genotoxic carcinogen benzo[a]pyrene, the non-genotoxic carcinogen bis(2-ethylhexyl) phthalate,and the non-carcinogen mannitol as controls. Upon exposure, RNA wasisolated and effects on whole genome mRNA expression were analysedusing DNA microarrays. Pathway analysis showed that several processesinvolved in genotoxicity, including DNA damage response, p53 pathwayand cell cycle checkpoints, were modulated by the PAs. Comparison ofthe array data with transcriptome data obtained by others upon exposureof HepaRG to various model hepatocarcinogens showed that eachof the PAs used in the present study generated a gene expression profilethat is characteristic for genotoxic carcinogens.

M3 - Abstract

SP - 1480

ER -