Induction of sister chromatid exchange by acrylamide and glycidamide in human lymphocytes: Role of polymorphisms in detoxification and DNA-repair genes in the genotoxicity of glycidamide

Marta Pingarilho, Nuno G. Oliveira, Célia Martins, Bruno Costa Gomes, Ana Sofia Fernandes, Vanda Martins, Anatalia Labilloy, João Pereira de Lima, José Rueff, Jorge Francisco Gaspar

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Abstract

Acrylamide (AA) is a probable human carcinogen generated in carbohydrate-rich foodstuffs upon heating. Glycidamide (GA), formed via epoxidation, presumably mediated by cytochrome P450 2E1, is considered to be the active metabolite that plays a central role in the genotoxicity of AA. The aim of this work was to evaluate the cytogenetic damage induced by AA and GA in cultured human lymphocytes by use of the sister chromatid exchange (SCE) assay. Furthermore, this report addresses the role of individual genetic polymorphisms in key genes involved in detoxification and DNA-repair pathways (BER, NER, HRR and NHEJ) on the induction of SCE by GA. While AA induced the number of SCE/metaphase only slightly, especially for the highest concentration tested (2000 mu M) markedly induced SCEs in a concentration-dependent manner up to concentrations of 750 mu M, leading to an increase in SCEs of up to about 10-fold compared with controls. By combining DNA damage in GA-treated lymphocytes and data on polymorphisms, associations between the induction of SCEs with GSTP1 (Ile105Val) and GSTA2 (Glu210Ala) genotypes are suggested. (c) 2013 Elsevier B.V. All rights reserved.
Original languageEnglish
Pages (from-to)1-7
Number of pages8
JournalMutation Research-Genetic Toxicology And Environmental Mutagenesis
Volume752
Issue number1-2
DOIs
Publication statusPublished - 15 Apr 2013

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Sister Chromatid Exchange
Acrylamide
DNA Repair
Lymphocytes
Genes
Cytochrome P-450 CYP2E1
Genetic Polymorphisms
Metaphase
Cytogenetics
Carcinogens
Heating
DNA Damage
Genotype
Carbohydrates
glycidamide

Cite this

@article{9299d4a2eca04821b4045dbf0a8308c2,
title = "Induction of sister chromatid exchange by acrylamide and glycidamide in human lymphocytes: Role of polymorphisms in detoxification and DNA-repair genes in the genotoxicity of glycidamide",
abstract = "Acrylamide (AA) is a probable human carcinogen generated in carbohydrate-rich foodstuffs upon heating. Glycidamide (GA), formed via epoxidation, presumably mediated by cytochrome P450 2E1, is considered to be the active metabolite that plays a central role in the genotoxicity of AA. The aim of this work was to evaluate the cytogenetic damage induced by AA and GA in cultured human lymphocytes by use of the sister chromatid exchange (SCE) assay. Furthermore, this report addresses the role of individual genetic polymorphisms in key genes involved in detoxification and DNA-repair pathways (BER, NER, HRR and NHEJ) on the induction of SCE by GA. While AA induced the number of SCE/metaphase only slightly, especially for the highest concentration tested (2000 mu M) markedly induced SCEs in a concentration-dependent manner up to concentrations of 750 mu M, leading to an increase in SCEs of up to about 10-fold compared with controls. By combining DNA damage in GA-treated lymphocytes and data on polymorphisms, associations between the induction of SCEs with GSTP1 (Ile105Val) and GSTA2 (Glu210Ala) genotypes are suggested. (c) 2013 Elsevier B.V. All rights reserved.",
keywords = "BREAST-CANCER SUSCEPTIBILITY, CYTOGENETIC DAMAGE, IN-VITRO, RISK, GLUTATHIONE S-TRANSFERASES, DIETARY ACRYLAMIDE, DNA-repair polymorphisms, Sister chromatid exchange, Detoxification, Acrylamide, Glycidamide, HUMAN BLOOD, CYTOCHROME-P450 2E1, PORTUGUESE POPULATION, COMMON VARIANTS",
author = "Marta Pingarilho and Oliveira, {Nuno G.} and C{\'e}lia Martins and Gomes, {Bruno Costa} and Fernandes, {Ana Sofia} and Vanda Martins and Anatalia Labilloy and {de Lima}, {Jo{\~a}o Pereira} and Jos{\'e} Rueff and Gaspar, {Jorge Francisco}",
year = "2013",
month = "4",
day = "15",
doi = "10.1016/j.mrgentox.2012.12.013",
language = "English",
volume = "752",
pages = "1--7",
journal = "Mutation Research-Genetic Toxicology And Environmental Mutagenesis",
issn = "1383-5718",
publisher = "Elsevier Science B.V., Inc",
number = "1-2",

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TY - JOUR

T1 - Induction of sister chromatid exchange by acrylamide and glycidamide in human lymphocytes: Role of polymorphisms in detoxification and DNA-repair genes in the genotoxicity of glycidamide

AU - Pingarilho, Marta

AU - Oliveira, Nuno G.

AU - Martins, Célia

AU - Gomes, Bruno Costa

AU - Fernandes, Ana Sofia

AU - Martins, Vanda

AU - Labilloy, Anatalia

AU - de Lima, João Pereira

AU - Rueff, José

AU - Gaspar, Jorge Francisco

PY - 2013/4/15

Y1 - 2013/4/15

N2 - Acrylamide (AA) is a probable human carcinogen generated in carbohydrate-rich foodstuffs upon heating. Glycidamide (GA), formed via epoxidation, presumably mediated by cytochrome P450 2E1, is considered to be the active metabolite that plays a central role in the genotoxicity of AA. The aim of this work was to evaluate the cytogenetic damage induced by AA and GA in cultured human lymphocytes by use of the sister chromatid exchange (SCE) assay. Furthermore, this report addresses the role of individual genetic polymorphisms in key genes involved in detoxification and DNA-repair pathways (BER, NER, HRR and NHEJ) on the induction of SCE by GA. While AA induced the number of SCE/metaphase only slightly, especially for the highest concentration tested (2000 mu M) markedly induced SCEs in a concentration-dependent manner up to concentrations of 750 mu M, leading to an increase in SCEs of up to about 10-fold compared with controls. By combining DNA damage in GA-treated lymphocytes and data on polymorphisms, associations between the induction of SCEs with GSTP1 (Ile105Val) and GSTA2 (Glu210Ala) genotypes are suggested. (c) 2013 Elsevier B.V. All rights reserved.

AB - Acrylamide (AA) is a probable human carcinogen generated in carbohydrate-rich foodstuffs upon heating. Glycidamide (GA), formed via epoxidation, presumably mediated by cytochrome P450 2E1, is considered to be the active metabolite that plays a central role in the genotoxicity of AA. The aim of this work was to evaluate the cytogenetic damage induced by AA and GA in cultured human lymphocytes by use of the sister chromatid exchange (SCE) assay. Furthermore, this report addresses the role of individual genetic polymorphisms in key genes involved in detoxification and DNA-repair pathways (BER, NER, HRR and NHEJ) on the induction of SCE by GA. While AA induced the number of SCE/metaphase only slightly, especially for the highest concentration tested (2000 mu M) markedly induced SCEs in a concentration-dependent manner up to concentrations of 750 mu M, leading to an increase in SCEs of up to about 10-fold compared with controls. By combining DNA damage in GA-treated lymphocytes and data on polymorphisms, associations between the induction of SCEs with GSTP1 (Ile105Val) and GSTA2 (Glu210Ala) genotypes are suggested. (c) 2013 Elsevier B.V. All rights reserved.

KW - BREAST-CANCER SUSCEPTIBILITY

KW - CYTOGENETIC DAMAGE

KW - IN-VITRO

KW - RISK

KW - GLUTATHIONE S-TRANSFERASES

KW - DIETARY ACRYLAMIDE

KW - DNA-repair polymorphisms

KW - Sister chromatid exchange

KW - Detoxification

KW - Acrylamide

KW - Glycidamide

KW - HUMAN BLOOD

KW - CYTOCHROME-P450 2E1

KW - PORTUGUESE POPULATION

KW - COMMON VARIANTS

U2 - 10.1016/j.mrgentox.2012.12.013

DO - 10.1016/j.mrgentox.2012.12.013

M3 - Article

VL - 752

SP - 1

EP - 7

JO - Mutation Research-Genetic Toxicology And Environmental Mutagenesis

JF - Mutation Research-Genetic Toxicology And Environmental Mutagenesis

SN - 1383-5718

IS - 1-2

ER -