TY - JOUR
T1 - GENETIC POLYMORPHISMS IN DETOXIFICATION AND DNA REPAIR GENES AND SUSCEPTIBILITY TO GLYCIDAMIDE-INDUCED DNA DAMAGE
AU - Gaspar, Jorge Francisco Dias Rodrigues
AU - Rueff, José
AU - Martins, Célia Maria da Silva
PY - 2012/1/1
Y1 - 2012/1/1
N2 - Acrylamide (AA) is a probable human carcinogen formed in carbohydrate-rich foodstuffs upon heating. Glycidamide (GA), the AA metabolite formed by epoxidation, is considered the ultimate genotoxic agent. In this study, the in vitro genotoxic potential of AA and GA in human whole blood leukocytes was compared using the alkaline comet assay. Although AA did not induce significant DNA damage in the concentrations tested (up to 1000 mu M), GA markedly increased the percentage of tail DNA at concentrations >= 250 mu M. Further, this study addressed the role of genetic polymorphisms in key genes involved in metabolism and DNA repair pathways (BER, NER, HRR, and NHEJ) on GA-induced genotoxicity assessed by the alkaline comet assay. The results obtained suggested associations between DNA damage and polymorphisms of BER (MUTYH Gln335His and XRCC1 Gln399Arg) and NER (XPC Ala499Val) genes, either alone or in combination.
AB - Acrylamide (AA) is a probable human carcinogen formed in carbohydrate-rich foodstuffs upon heating. Glycidamide (GA), the AA metabolite formed by epoxidation, is considered the ultimate genotoxic agent. In this study, the in vitro genotoxic potential of AA and GA in human whole blood leukocytes was compared using the alkaline comet assay. Although AA did not induce significant DNA damage in the concentrations tested (up to 1000 mu M), GA markedly increased the percentage of tail DNA at concentrations >= 250 mu M. Further, this study addressed the role of genetic polymorphisms in key genes involved in metabolism and DNA repair pathways (BER, NER, HRR, and NHEJ) on GA-induced genotoxicity assessed by the alkaline comet assay. The results obtained suggested associations between DNA damage and polymorphisms of BER (MUTYH Gln335His and XRCC1 Gln399Arg) and NER (XPC Ala499Val) genes, either alone or in combination.
KW - BREAST-CANCER SUSCEPTIBILITY
KW - GENOTOXICITY
KW - HEMOGLOBIN ADDUCTS
KW - HUMAN-LYMPHOCYTES
KW - DIETARY ACRYLAMIDE INTAKE
KW - COMET ASSAY
KW - MAMMALIAN-CELLS
KW - RISK-ASSESSMENT
KW - PORTUGUESE POPULATION
KW - COMMON VARIANTS
U2 - 10.1080/15287394.2012.690709
DO - 10.1080/15287394.2012.690709
M3 - Article
C2 - 22788377
SN - 1528-7394
VL - 75
SP - 920
EP - 933
JO - Journal Of Toxicology And Environmental Health-Part A-Current Issues
JF - Journal Of Toxicology And Environmental Health-Part A-Current Issues
IS - 13-15
ER -