Genetic polymorphisms in detoxification and DNA repair genes and susceptibility to glycidamide-induced DNA damage.
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 μM), GA markedly increased the percentage of tail DNA at concentrations ≥250 μM. 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.
Department of Genetics, Faculty of Medical Sciences, New University of Lisbon (CIGMH), Lisboa, Portugal.
Marta
M
Pingarilho
Nuno G
NG
Oliveira
Célia
C
Martins
Ana Sofia
AS
Fernandes
João Pereira
JP
de Lima
José
J
Rueff
Jorge Francisco
JF
Gaspar
D020106:Acrylamide / Q000633:toxicity; D000328:Adult; D019943:Amino Acid Substitution; D002274:Carcinogens, Environmental / Q000633:toxicity; D004249:DNA Damage; D045647:DNA Glycosylases / Q000235:genetics* / Q000378:metabolism; D004260:DNA Repair / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D004852:Epoxy Compounds / Q000633:toxicity*; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D007962:Leukocytes / Q000378:metabolism; D008297:Male; D009153:Mutagens / Q000633:toxicity*; D009994:Osmolar Concentration; D020641:Polymorphism, Single Nucleotide; D011174:Portugal; D000076105:X-ray Repair Cross Complementing Protein 1; D055815:Young Adult
D002274:Carcinogens, Environmental; D004268:DNA-Binding Proteins; D004852:Epoxy Compounds; D009153:Mutagens; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human; C086984:XPC protein, human; D020106:Acrylamide; C071834:glycidamide; D045647:DNA Glycosylases; C061738:mutY adenine glycosylase