Association Study of the Frequencies of Spontaneous and Induced Chromosome Aberrations in Human Lymphocytes

Abstract

The data on the frequencies of chromosome aberrations in lymphocytes of peripheral blood of 99 volunteers depending on genotypes by genes of xenobiotics detoxification before and after γ-irradiation with the dose of 1 Gy in vitro are presented. The frequencies of aberrations were estimated by analyzing not less than 500–1,000 metaphases per person. The data of the cytogenetic analysis were compared with the results of PCR genotyping by the genes of xenobiotics detoxication (CYP1A1, CYP2D6, GSTM1, GSTT1, GSTP1, COMT, NAT2), genes of DNA repair (XRCC1, XPD, ERCC1, APEX1, RAD23B, OGG1, ATM) as well as by the genes of oxidative response and cell cycle regulation (SOD2, CAT, GCLC, MTHFR, Tp53). The frequency of spontaneous aberrations of chromosome type was reduced for homozygotes by the deletion of GSTM1 locus, especially for double homozygotes by the deletions of GSTM-GSTT1 genes. The mentioned frequency increased additively with the number of copies of the minor allele variants XPD*2251 G and XPD*862A of gene of excision repair XPD (p = 0.025). The frequency of γ-induced chromosome aberrations proved to be elevated for the carriers of a minor allele OGG1*977 G (p = 0.011). The significantly elevated number of γ-induced chromosome aberrations was also observed for the carriers of major alleles XRCC1*G1996 and XRCC1*C580 (p = 0.002). The frequency of γ-induced chromosome aberrations proved to be reduced for G/G homozygotes by a minor allele of poorly studied site CYPA1T606G: 0.094 ± 0.006 against 0.112 ± 0.002 for the carriers of allele T (p = 0.004). The results of meta-analysis of the data of 14 works on the effect of genotype by GSTM1 locus on the frequency of cytogenetic anomalies in the control and exposed populations are discussed.