title: Influence of genetic polymorphisms on biomarkers of exposure and effects in children living in Upper Silesia.
abstract: This article is a follow-up to our previous molecular epidemiology studies on the DNA damage in children from the Upper Silesia region of Poland. It is expected that metabolic and DNA repair gene polymorphisms may modulate individual susceptibility to environmental exposure. In this study, we investigate the association between polymorphisms of metabolising (CYP2D, EPHX1, GSTM1, GSTP1, GSTT1, NAT2) and DNA repair (XPD, XRCC1, XRCC3) genes and selected biomarkers of exposure and effect such as levels of 1-hydroxypyrene (1-OHP) and urinary mutagenicity, aromatic DNA adducts, sister chromatid exchange (SCE) and micronuclei (MN) in 74 children. Both 1-OHP concentration and urinary mutagenicity tested by TA98+S9 were significantly higher in individuals with EPHX1 (exon 4) Arg/Arg genotype than in individuals with other genotype. The EPHX1 (exon 3) significantly affected urinary mutagenicity tested with strain YG1024+S9. The urinary mutagenicity in individuals with Tyr/Tyr homozygotes was lower than in individuals with Tyr/His and His/His (1057±685 vs. 1432±1003 revertants/mol creatinine). XRCC3 Met/Met genotype was associated with significantly higher levels of 1-OHP in urine compared with only The/Met genotype. The PAH-DNA adduct levels in the subgroup with GSTM1 null genotype was 2-fold higher than in individuals with GSTM1 active (7.06±5.12 vs. 13.14±9.81 adduct/10(8) nucleotides). The mean level of aromatic DNA adducts in children with deletion of the GSTT1 gene was significantly higher compared with individuals with that gene present (8.03±6.23 vs. 14.66±10.70 adduct/10(8) nucleotides). Also the carriers of the XPD Lys/Lys genotype showed higher levels of DNA adducts than heterozygotes (13.16±9.70 vs. 6.81±5.86 adducts/10(8) nucleotides). Children carrying the XRCC3-241 Met/Met genotype exhibited a higher number of SCE in peripheral blood lymphocytes than carriers of Thr/Met allele (8.15±0.86 vs. 7.62±0.79 SCE/cell). It was also observed that children with the GSTP1 slow conjugator had significantly elevated MN in peripheral blood lymphocytes compared with fast conjugator (4.23±3.49 vs. 6.56±5.00 MN/1000 cells).
authors.affiliation: Department of Genetic Toxicology, Institute of Occupational Medicine and Environmental Health, Koscielna 13 Street, 41-200 Sosnowiec, Poland. d.mielzynska@imp.sosnowiec.pl
authors.forename: Danuta
authors.initials: D
authors.lastname: Mielzynska-Svach
authors.forename: Ewa
authors.initials: E
authors.lastname: Blaszczyk
authors.forename: Dorota
authors.initials: D
authors.lastname: Butkiewicz
authors.forename: Julia
authors.initials: J
authors.lastname: Durzynska
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Rydzanicz
mesh_terms: D000293:Adolescent; D000429:Alcohol Oxidoreductases / Q000235:genetics; D001191:Arylamine N-Acetyltransferase / Q000235:genetics; D015415:Biomarkers / Q000032:analysis*; D002648:Child; D002675:Child, Preschool; D018736:DNA Adducts / Q000032:analysis; D004260:DNA Repair / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D004781:Environmental Exposure / Q000032:analysis*; D004851:Epoxide Hydrolases / Q000235:genetics; D005260:Female; D051549:Glutathione S-Transferase pi / Q000235:genetics; D005982:Glutathione Transferase / Q000235:genetics; D006720:Homozygote; D006801:Humans; D008297:Male; D015162:Micronucleus Tests; D011044:Poland; D011084:Polycyclic Aromatic Hydrocarbons / Q000032:analysis; D011110:Polymorphism, Genetic; D011721:Pyrenes / Q000652:urine; D012854:Sister Chromatid Exchange; D000076105:X-ray Repair Cross Complementing Protein 1; D051759:Xeroderma Pigmentosum Group D Protein / Q000235:genetics
chemical_list: D000429:Alcohol Oxidoreductases; D001191:Arylamine N-Acetyltransferase; D015415:Biomarkers; D018736:DNA Adducts; D004268:DNA-Binding Proteins; D004851:Epoxide Hydrolases; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; D011084:Polycyclic Aromatic Hydrocarbons; D011721:Pyrenes; D000076105:X-ray Repair Cross Complementing Protein 1; D051759:Xeroderma Pigmentosum Group D Protein; C110901:X-ray repair cross complementing protein 3; C000619371:XRCC1 protein, human; C095911:polycyclic aromatic hydrocarbons-DNA adduct; C478900:NAT2 protein, human; C413545:glutathione S-transferase T1; C496556:GSTP1 protein, human; C522330:EPHX1 protein, human; C497292:ERCC2 protein, human; C033146:1-hydroxypyrene