Influence of DNA repair gene polymorphisms on the yield of chromosomal aberrations.
We evaluated the influence of several DNA repair gene polymorphisms on the frequency of chromosomal aberrations (CAs) analyzed in peripheral lymphocytes, using the fluorescence in situ hybridization technique. The CA data were obtained from an earlier study of 84 healthy nonsmokers (48 women and 36 men) carefully characterized for indoor radon exposure. The frequency of translocations showed a wide interindividual variability, which was only partly explained by age. To investigate the potential role of DNA repair polymorphisms in this variation, genotypes of DNA repair genes OGG1 (codon 326), XPD (codon 751), XRCC1 (X-ray repair cross-complementing group 1) (codons 194, 280, and 399), and XRCC3 (X-ray repair cross-complementing group 3) (codon 241) were determined from leukocyte DNA using polymerase chain reaction-based methods. Negative binomial regression models were applied to evaluate the effect of the polymorphisms and other factors (age, gender, radon exposure, and medical exposure) on the frequency of CAs. No interactions between genotypes and radon, medical exposure, or gender were found. Carriers of the XRCC1 codon 280His variant allele had a two-fold increase (frequency ratio [FR] = 2.01, 95% confidence interval [CI] = 1.01-3.98; P = 0.046) in unstable exchanges (dicentrics and ring chromosomes). In addition, the XRCC3 codon 241 homozygous variant genotype (Met/Met) was associated with an increase (FR = 1.70, 95% CI = 1.06-2.74; P = 0.028) in two-way translocations when age was taken into account in the analysis. Our data suggest that the XRCC1 280His and XRCC3 241Met alleles affect individual CA levels, most probably via influencing the DNA repair phenotype.
Kiuru
Anne
A
Department of Research and Environmental Surveillance, STUK-Radiation and Nuclear Safety Authority, FIN-00881 Helsinki, Finland. anne.kiuru@stuk.fi
Lindholm
Carita
C
Heilimo
Iiris
I
Ceppi
Marcello
M
Koivistoinen
Armi
A
Ilus
Taina
T
Hirvonen
Ari
A
Norppa
Hannu
H
Salomaa
Sisko
S
D000367:Age Factors; D002869:Chromosome Aberrations; D003062:Codon; D045647:DNA Glycosylases / Q000235:genetics; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006720:Homozygote; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D010641:Phenotype; D011110:Polymorphism, Genetic; D011886:Radon; D012907:Smoking; D014178:Translocation, Genetic; D000076105:X-ray Repair Cross Complementing Protein 1; D051759:Xeroderma Pigmentosum Group D Protein / Q000235:genetics
D003062:Codon; D004268:DNA-Binding Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; C110901:X-ray repair cross complementing protein 3; C000619371:XRCC1 protein, human; D045647:DNA Glycosylases; C479058:oxoguanine glycosylase 1, human; D051759:Xeroderma Pigmentosum Group D Protein; C497292:ERCC2 protein, human; D011886:Radon