title: Expression of XRCC5 in peripheral blood lymphocytes is upregulated in subjects from a heavily polluted region in the Czech Republic.
abstract: Air pollution causes oxidative damage to macromolecules, chromosomal aberrations and changes in gene expression. We investigated the levels of oxidative stress markers [8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), 15-F(2t)-isoprostane (15-F2t-IsoP), protein carbonyls] and cytogenetic parameters [genomic frequency of translocations (F(G)/100), percentage of aberrant cells (%AB.C.) and acentric fragments (ace)] in subjects living in Prague and in the heavily polluted Ostrava region. We also compared the expression of genes participating in base excision repair (BER) and non-homologous end-joining (NHEJ). We analyzed 64 subjects from Prague and 75 subjects from Ostrava. We measured oxidative stress markers by ELISA, cytogenetic parameters by fluorescence in situ hybridization and gene expression by quantitative PCR. The levels of air pollutants (benzo[a]pyrene, B[a]P; carcinogenic polycyclic aromatic hydrocarbons, c-PAHs; benzene) measured by personal monitors were significantly elevated in Ostrava compared to Prague (p<0.001). Despite this fact, we observed no differences in biomarkers of oxidative stress between the two locations. Moreover, subjects from Ostrava were less likely to have above-median levels of %AB.C. (OR; 95% CI: 0.18; 0.05-0.67; p=0.010). Multivariate analyses revealed that subjects living in Ostrava had increased odds of having above-median levels of XRCC5 expression (OR; 95% CI: 3.33; 1.03-10.8; q=0.046). Above-median levels of 8-oxodG were associated with decreased levels of vitamins C (OR; 95% CI: 0.37; 0.16-0.83; p=0.016) and E (OR; 95% CI: 0.25; 0.08-0.75; p=0.013), which were elevated in subjects from Ostrava. We suggest that air pollution by c-PAHs affects XRCC5 gene expression, which probably protects subjects from Ostrava against the induction of a higher frequency of translocations; elevated vitamin C and E levels in the Ostrava subjects decrease the levels of 8-oxodG.
authors.affiliation: Laboratory of Genetic Ecotoxicology, Institute of Experimental Medicine AS CR, Videnska 1083, 142 20 Prague, Czech Republic. prossner@biomed.cas.cz
authors.forename: Pavel
authors.initials: P
authors.lastname: Rossner
authors.forename: Katerina
authors.initials: K
authors.lastname: Uhlirova
authors.forename: Olena
authors.initials: O
authors.lastname: Beskid
authors.forename: Andrea
authors.initials: A
authors.lastname: Rossnerova
authors.forename: Vlasta
authors.initials: V
authors.lastname: Svecova
authors.forename: Radim J
authors.initials: RJ
authors.lastname: Sram
mesh_terms: D000328:Adult; D000397:Air Pollution; D002869:Chromosome Aberrations; D018153:Czech Republic; D004265:DNA Helicases / Q000378:metabolism*; D004260:DNA Repair; D006801:Humans; D000072200:Ku Autoantigen; D008214:Lymphocytes / Q000737:chemistry; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D015854:Up-Regulation
chemical_list: D004265:DNA Helicases; C106893:XRCC5 protein, human; D000072200:Ku Autoantigen