Estragole: A weak direct-acting food-borne genotoxin and potential carcinogen

Célia Martins, Raquel Cação, Kathleen J. Cole, David H. Phillips, A Laires, J. Rueff, A. S. Rodrigues

Research output: Contribution to journalArticle

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Abstract

We evaluated the genotoxicity of the food-flavouring agent estragole in V79 cells using the sister chromatid exchange (SCE) assay and the alkaline comet assay. Unexpectedly, we observed an increase in SCE without an exogenous biotransformation system (S9) and a decrease in its presence. Positive results were also observed in the alkaline comet assay without S9, indicating DNA strand breakage. To ascertain repair of damage, we performed the comet assay in V79 cells after two hours of recovery, and observed a reduction of the genotoxic response. Estragole did not produce strand breaks in plasmid DNA in vitro. We then evaluated the formation of DNA adducts in V79 cells by use of the P-32-postlabelling assay and detected a dose-dependent formation of DNA adducts, which may be responsible for its genotoxicity. We then assayed estragole in the comet assay with two CHO cell lines, a parental AA8 cell line, and an XRCC1-deficient cell line, EM9. Results confirmed the genotoxicity of estragole without biotransformation in both cell lines, although the genotoxicity in EM9 cells compared with that in AA8 cells was not significantly different, suggesting that the XRCC1 protein is not involved in the repair of estragole-induced lesions. Estragole induces apoptosis, but only with high doses (2000 mu M), and after long treatment periods (24 h). Overall, our results suggest that estragole, besides being metabolized to genotoxic metabolites, is a weak direct-acting genotoxin that forms DNA adducts.
Original languageEnglish
Pages (from-to)86-92
Number of pages7
JournalMutation Research-Genetic Toxicology And Environmental Mutagenesis
Volume747
Issue number1
DOIs
Publication statusPublished - 2012

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Mutagens
Carcinogens
Comet Assay
Food
DNA Adducts
Cell Line
Sister Chromatid Exchange
Biotransformation
Flavoring Agents
CHO Cells
DNA
estragole
Plasmids
Apoptosis
Proteins

Cite this

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title = "Estragole: A weak direct-acting food-borne genotoxin and potential carcinogen",
abstract = "We evaluated the genotoxicity of the food-flavouring agent estragole in V79 cells using the sister chromatid exchange (SCE) assay and the alkaline comet assay. Unexpectedly, we observed an increase in SCE without an exogenous biotransformation system (S9) and a decrease in its presence. Positive results were also observed in the alkaline comet assay without S9, indicating DNA strand breakage. To ascertain repair of damage, we performed the comet assay in V79 cells after two hours of recovery, and observed a reduction of the genotoxic response. Estragole did not produce strand breaks in plasmid DNA in vitro. We then evaluated the formation of DNA adducts in V79 cells by use of the P-32-postlabelling assay and detected a dose-dependent formation of DNA adducts, which may be responsible for its genotoxicity. We then assayed estragole in the comet assay with two CHO cell lines, a parental AA8 cell line, and an XRCC1-deficient cell line, EM9. Results confirmed the genotoxicity of estragole without biotransformation in both cell lines, although the genotoxicity in EM9 cells compared with that in AA8 cells was not significantly different, suggesting that the XRCC1 protein is not involved in the repair of estragole-induced lesions. Estragole induces apoptosis, but only with high doses (2000 mu M), and after long treatment periods (24 h). Overall, our results suggest that estragole, besides being metabolized to genotoxic metabolites, is a weak direct-acting genotoxin that forms DNA adducts.",
keywords = "ENZYME LEVELS, Genotoxicity, POST-LABELING ANALYSIS, HEPG2 CELLS, COMET ASSAY, Apoptosis, NATURALLY-OCCURRING ALKENYLBENZENES, Sister chromatid exchange, Estragole, XRCC1, INDIVIDUAL CELLS, MOUSE-LIVER, DNA adducts, DNA-ADDUCTS, PRIMARY HUMAN HEPATOCYTES, IN-VIVO",
author = "C{\'e}lia Martins and Raquel Ca{\cc}{\~a}o and Cole, {Kathleen J.} and Phillips, {David H.} and A Laires and J. Rueff and Rodrigues, {A. S.}",
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Estragole: A weak direct-acting food-borne genotoxin and potential carcinogen. / Martins, Célia; Cação, Raquel; Cole, Kathleen J.; Phillips, David H.; Laires, A; Rueff, J.; Rodrigues, A. S.

In: Mutation Research-Genetic Toxicology And Environmental Mutagenesis, Vol. 747, No. 1, 2012, p. 86-92.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Estragole: A weak direct-acting food-borne genotoxin and potential carcinogen

AU - Martins, Célia

AU - Cação, Raquel

AU - Cole, Kathleen J.

AU - Phillips, David H.

AU - Laires, A

AU - Rueff, J.

AU - Rodrigues, A. S.

PY - 2012

Y1 - 2012

N2 - We evaluated the genotoxicity of the food-flavouring agent estragole in V79 cells using the sister chromatid exchange (SCE) assay and the alkaline comet assay. Unexpectedly, we observed an increase in SCE without an exogenous biotransformation system (S9) and a decrease in its presence. Positive results were also observed in the alkaline comet assay without S9, indicating DNA strand breakage. To ascertain repair of damage, we performed the comet assay in V79 cells after two hours of recovery, and observed a reduction of the genotoxic response. Estragole did not produce strand breaks in plasmid DNA in vitro. We then evaluated the formation of DNA adducts in V79 cells by use of the P-32-postlabelling assay and detected a dose-dependent formation of DNA adducts, which may be responsible for its genotoxicity. We then assayed estragole in the comet assay with two CHO cell lines, a parental AA8 cell line, and an XRCC1-deficient cell line, EM9. Results confirmed the genotoxicity of estragole without biotransformation in both cell lines, although the genotoxicity in EM9 cells compared with that in AA8 cells was not significantly different, suggesting that the XRCC1 protein is not involved in the repair of estragole-induced lesions. Estragole induces apoptosis, but only with high doses (2000 mu M), and after long treatment periods (24 h). Overall, our results suggest that estragole, besides being metabolized to genotoxic metabolites, is a weak direct-acting genotoxin that forms DNA adducts.

AB - We evaluated the genotoxicity of the food-flavouring agent estragole in V79 cells using the sister chromatid exchange (SCE) assay and the alkaline comet assay. Unexpectedly, we observed an increase in SCE without an exogenous biotransformation system (S9) and a decrease in its presence. Positive results were also observed in the alkaline comet assay without S9, indicating DNA strand breakage. To ascertain repair of damage, we performed the comet assay in V79 cells after two hours of recovery, and observed a reduction of the genotoxic response. Estragole did not produce strand breaks in plasmid DNA in vitro. We then evaluated the formation of DNA adducts in V79 cells by use of the P-32-postlabelling assay and detected a dose-dependent formation of DNA adducts, which may be responsible for its genotoxicity. We then assayed estragole in the comet assay with two CHO cell lines, a parental AA8 cell line, and an XRCC1-deficient cell line, EM9. Results confirmed the genotoxicity of estragole without biotransformation in both cell lines, although the genotoxicity in EM9 cells compared with that in AA8 cells was not significantly different, suggesting that the XRCC1 protein is not involved in the repair of estragole-induced lesions. Estragole induces apoptosis, but only with high doses (2000 mu M), and after long treatment periods (24 h). Overall, our results suggest that estragole, besides being metabolized to genotoxic metabolites, is a weak direct-acting genotoxin that forms DNA adducts.

KW - ENZYME LEVELS

KW - Genotoxicity

KW - POST-LABELING ANALYSIS

KW - HEPG2 CELLS

KW - COMET ASSAY

KW - Apoptosis

KW - NATURALLY-OCCURRING ALKENYLBENZENES

KW - Sister chromatid exchange

KW - Estragole

KW - XRCC1

KW - INDIVIDUAL CELLS

KW - MOUSE-LIVER

KW - DNA adducts

KW - DNA-ADDUCTS

KW - PRIMARY HUMAN HEPATOCYTES

KW - IN-VIVO

U2 - 10.1016/j.mrgentox.2012.04.009

DO - 10.1016/j.mrgentox.2012.04.009

M3 - Article

VL - 747

SP - 86

EP - 92

JO - Mutation Research-Genetic Toxicology And Environmental Mutagenesis

JF - Mutation Research-Genetic Toxicology And Environmental Mutagenesis

SN - 1383-5718

IS - 1

ER -