title: Genetic polymorphisms of genes involved in DNA repair and metabolism influence micronucleus frequencies in human peripheral blood lymphocytes.
abstract: The cytokinesis-block micronucleus cytome (CBMNCyt) assay is a widely used technique for measuring DNA damage in human populations. The formation of micronuclei (MN) in dividing cells can result from chromosome breakage due to unrepaired or mis-repaired DNA lesions or chromosome malsegregation due to mitotic malfunction. The sensitivity of the MN assay to polymorphisms in various genes involved in DNA repair, activation/deactivation of carcinogens/chemicals/drugs/alcohol, folate metabolism pathway and micronutrient transport has been extensively reported in the literature. MN frequency is also an important index for determining DNA repair efficiency phenotype (including mis-repair), response to environmental exposure and identifying various dietary factors required for optimal genome stability. The aim of the present study is to review the reported in vivo associations between genotype and MN frequency in humans taking into considerations the presence of interactions with nutrients levels and/or exposure to genotoxins. One hundred and eleven publications linking MN frequency in peripheral blood lymphocytes to gene polymorphism were retrieved from PubMed. After applying exclusion criteria, only 37 studies were evaluated in the present review. Polymorphisms in XRCC1 (Arg280His), ERCC2 (Lys751Gln), CYP2E1 (c1/c2) and MTR (A2756G) were consistently associated with the MN formation. These results contribute substantial evidence to the hypothesis that genotype may influence MN frequency in human cells.
authors.affiliation: CSIRO Food and Nutritional Sciences, Gate 13, Kintore Avenue, PO Box 10041, Adelaide, South Australia 5000, Australia. varinderpal.dhillon@csiro.au
authors.forename: Varinderpal S
authors.initials: VS
authors.lastname: Dhillon
authors.forename: Philip
authors.initials: P
authors.lastname: Thomas
authors.forename: G
authors.initials: G
authors.lastname: Iarmarcovai
authors.forename: Micheline
authors.initials: M
authors.lastname: Kirsch-Volders
authors.forename: Stefano
authors.initials: S
authors.lastname: Bonassi
authors.forename: Michael
authors.initials: M
authors.lastname: Fenech
mesh_terms: D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics; D004260:DNA Repair / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics; D004781:Environmental Exposure; D005260:Female; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D048629:Micronuclei, Chromosome-Defective / Q000139:chemically induced*; D015162:Micronucleus Tests; D009153:Mutagens / Q000633:toxicity*; D011110:Polymorphism, Genetic; D058978:Reduced Folate Carrier Protein / Q000235:genetics; D000076105:X-ray Repair Cross Complementing Protein 1; D051759:Xeroderma Pigmentosum Group D Protein / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; D009153:Mutagens; D058978:Reduced Folate Carrier Protein; C548699:SLC19A1 protein, human; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human; D019392:Cytochrome P-450 CYP2E1; D051759:Xeroderma Pigmentosum Group D Protein; C497292:ERCC2 protein, human