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1.
Genetika ; 47(11): 1536-44, 2011 Nov.
Article in Russian | MEDLINE | ID: mdl-22332411

ABSTRACT

Genotypic associations were studied for the frequency of chromosome aberrations in human peripheral blood lymphocytes. Cytogenetic analysis (1000 metaphase plate per individual) and genotyping at 19 sites of genes involved in detoxification and DNA repair were performed in a sample of 83 Chernobyl liquidators and a matched control sample of 96 volunteers. In either sample, the frequency of chromosome aberrations was higher in carriers of the minor alleles of the XPD gene (sites 2251T > G and 862G > A) and the positive genotypes of the GSTM1-GSTT1 genes. The highest frequency of chromosome aberrations was observed in carriers of a combined genotype including at least one minor allele of the XPD sites + at least one insertion in the GSTM1-GSTT1 genes. The high-risk genotype, which had a prevalence of 64%, was strongly associated with a higher frequency of chromosome aberrations in both volunteers (OR = 6.9, P = 0.008) and Chernobyl liquidators (OR = 5.6, P = 0.002).


Subject(s)
Chernobyl Nuclear Accident , Chromosome Aberrations , Glutathione Transferase/genetics , Xeroderma Pigmentosum Group D Protein/genetics , Adult , Alleles , Female , Gene Frequency , Genes , Genotype , Humans , Lymphocytes/radiation effects , Male , Polymorphism, Genetic , Radiation, Ionizing , Recombinational DNA Repair/genetics , Young Adult
2.
Radiats Biol Radioecol ; 50(3): 340-4, 2010.
Article in Russian | MEDLINE | ID: mdl-20734807

ABSTRACT

The data on the variability of an elevated level of the frequencies of chromosome aberrations for a group of liquidators of the Chernobyl Nuclear Station accident depending on genotypes by candidate loci are presented. The genotyping was carried out by sites, which previously showed the associations with the cytogenetic variability in control experiments. It was shown that, for a group of liquidators heterozygote by site SOD2 C47T, the control level of the frequency of chromosome aberrations is not exceeded significantly. At the tendency level, the frequency of aberrations for liquidators was reduced for double homozygotes by deletions of genes GSTM1-GSTT1 and for homozygotes by the minor allele of site CYP1A1 T606G that is in an accordance with the results of experiments with the control sampling. The elevated level of chromosome aberrations for liquidators, as a whole, is observed for genotypes, which are characteristic of an elevated level of spontaneous aberrations, and it does not completely correspond to genotypes with the elevated radiosensitivity of chromosomes.


Subject(s)
Chernobyl Nuclear Accident , Chromosome Aberrations , Gamma Rays , Lymphocytes/radiation effects , Alleles , Cells, Cultured , Cytochrome P-450 CYP1A1/genetics , DNA/radiation effects , Gene Frequency , Genotype , Glutathione Transferase/genetics , Heterozygote , Homozygote , Humans , Lymphocytes/chemistry , Lymphocytes/enzymology , Male , Middle Aged , Occupational Exposure , Polymorphism, Genetic , Superoxide Dismutase/genetics
3.
Radiats Biol Radioecol ; 50(6): 656-62, 2010.
Article in Russian | MEDLINE | ID: mdl-21434392

ABSTRACT

For 99 healthy volunteers, the frequencies of spontaneous and y-induced (1 Gy in vitro) chromosome aberrations in blood lymphocytes were compared with the results of PCR-genotyping by 8 repair genes: XRCC1, XPD, ERCC1, APEXI, RAD23B, OGG1, ATM, Tp53 (in all, 10 polymorphic sites). The frequency of spontaneous aberrations of chromosome type increased additively with the number of copies of minor allele of excision repair gene XPD variant *2251G and *862A D (p = 0.025). The frequency of gamma-induced chromosome aberrations proved to be elevated for the carriers of a minor allele OGG1*977G (p = 0.011). The significantly elevated number of gamma-induced chromosome aberrations was also observed for the carriers of major alleles XRCC1*G1996 and XRCC1*C589 (p = 0.002).


Subject(s)
Chromosome Aberrations/radiation effects , DNA Repair/radiation effects , Gamma Rays , Lymphocytes/radiation effects , Polymorphism, Genetic , Adult , Alleles , Cytogenetic Analysis , DNA Repair/genetics , Genotype , Humans , In Vitro Techniques , Male , Young Adult
4.
Genetika ; 46(12): 1678-84, 2010 Dec.
Article in Russian | MEDLINE | ID: mdl-21434421

ABSTRACT

Associations of polymorphism of seven detoxification genes and three genes of oxidative response with the frequency of chromosome aberrations in human peripheral blood lymphocytes were studied. The genotyping data were correlated with the frequencies of spontaneous and gamma-induced (1 Gy in vitro) chromosome aberrations estimated for a group of healthy donors (97 males under 25 years of age) by analyzing 500-1000 metaphase cells per individual. The spontaneous level of aberrations of the chromosomal type was reduced in homozygotes for the GSTM1 locus deletion, and especially in double homozygotes for deletions of the GSTM1 and GSTT1 genes. The frequency of gamma-induced chromosome aberrations was reduced in G/G homozygotes for the minor allele of the poorly studied CYP1A1 T606G site: 0.094 +/- 0.006 against 0.112 +/- 0.002 for T allele carriers (P = 0.004). Linkage of the T606G site with well known and functionally important sites of the CYP1A1 gene (A4889G, T3801C) was analyzed.


Subject(s)
Chromosome Aberrations , Genetic Loci , Lymphocytes/ultrastructure , Adult , Aryl Hydrocarbon Hydroxylases/genetics , Catalase/genetics , Gamma Rays , Glutamate-Cysteine Ligase/genetics , Glutathione Transferase/genetics , Humans , In Vitro Techniques , Inactivation, Metabolic/genetics , Lymphocytes/metabolism , Lymphocytes/radiation effects , Male , Methylenetetrahydrofolate Reductase (NADPH2)/genetics , Mutagenesis , Oxidation-Reduction , Polymorphism, Genetic , Superoxide Dismutase/genetics , Xenobiotics/metabolism , Young Adult
5.
Radiats Biol Radioecol ; 49(5): 543-51, 2009.
Article in Russian | MEDLINE | ID: mdl-19947517

ABSTRACT

Here presented the data on the frequencies of chromosome aberrations in lymphocytes of peripheral blood of 97 volunteers depending on genotypes by genes of xenobiotics detoxication before and after gamma-irradiation with dose of 1 Gy in vitro. The frequencies of aberrations were estimated by analyzing not less than 500-1000 metaphases per person. The data of cytogenetic analysis were compared with the results of PCR-genotyping of loci GSTM1, GSTT1, GSTP1, CYP1A1, CYP2D6, NAT2, and MTHFR. The significant differences by the frequencies of aberrations between "single-locus" genotypes were not found except for GSTM1 locus, for which the enhanced frequency of spontaneous aberrations of chromosome type in "positive" genotypes compared to "zero" ones, i.e., homozygotes by deletion (p = 0.04) was observed. The minimum frequency of spontaneous aberrations of chromosome type was recorded for carriers of double homozygotes by deletion of GSTM1-GSTT1: 0.0006 +/- 0.0003 against 0.0027 +/- 0.0003 for the rest of genotypes (p = 0.016 by the Mann-Witney test). The frequency of gamma-induced chromosome aberrations was correlated with the total amount of minor alleles in loci GSTP1, NAT2, and MTHFR (r = 0.25 at p = 0.0065).


Subject(s)
Arylamine N-Acetyltransferase/genetics , Chromosome Aberrations , Gamma Rays , Glutathione Transferase/genetics , Methylenetetrahydrofolate Reductase (NADPH2)/genetics , Polymorphism, Genetic , Adult , Alleles , Cells, Cultured , Humans , Lymphocytes/radiation effects , Xenobiotics/metabolism
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