title: Influence of GSTM1 and NAT2 genotypes on placental DNA adducts in an environmentally exposed population.
abstract: The placenta bulky DNA adducts have been studied in relation to metabolic genotypes for glutathione S-transferase M1 (GSTM1) and N-acetyl transferase 2 (NAT2) in 158 mothers (113 nonsmokers and 45 smokers) living in two regions with different annual average air pollution levels of sulphur dioxide, nitrogen oxides, particulate matter < 10 microns, and polycyclic aromatic hydrocarbons. One region was the district of Teplice as the polluted industrial region with mines and brown coal power plants, and the other was the district of Prachatice, an agricultural region without heavy industry. DNA adduct levels were determined by using a butanol extraction enrichment procedure of 32P-postlabeling. GSTM1 and NAT2 genotypes were studied by using polymerase chain reaction. The total DNA adduct levels included a diagonal radioactive zone (DRZ) and one distinct spot outside DRZ (termed X), which was detected in almost all placenta samples and correlated with DRZ (r = .682; P < .001). We found the total DNA adduct levels 2.12 +/- 1.46 (0.04-7.70) and 1.48 +/- 1.09 (0.11-4.98) adducts per 10(8) nucleotides for Teplice and Prachatice districts, respectively, indicating significant differences between both regions studied (P = .004). Elevated DNA adduct levels were found in smoking mothers (10 or more cigarettes per day) by comparison with nonsmoking mothers (3.21 +/- 1.39 versus 1.32 +/- 0.88 adducts per 10(8) nucleotides; P < .001). Placental DNA adduct levels in smokers correlated with cotinine measured in plasma (r = .432; P = .003). This relation indicates that cigarette smoking could be predominantly responsible for DNA adduct formation in placentas of smoking mothers. DNA adduct levels were evaluated separately for non-smokers (1.50 +/- 1.00 vs. 1.09 +/- 0.66 adducts/10(8) nucleotides for the Teplice and Prachatice districts, respectively; P = .046) and smokers (3.35 +/- 1.47 vs. 2.91 +/- 1.20 adducts/10(8) nucleotides for Teplice and Prachatice districts, respectively; P = .384) to exclude the effect of active cigarette smoking on the district variation. These findings indicate that the effect of the environmental pollution in cigarette smokers is practically overlapped by tobacco exposure. No seasonal variation was observed for DNA adduct levels in the overall population studied and no relation between total DNA adduct levels in placenta and levels of vitamins A, C, and E in venous and cord blood was found. A positive GSTM1 genotype was detected in 78 subjects, while negative GSTM1 genotype was found in 80 subjects. Higher DNA adduct levels were detected in the group with GSTM1-negative genotype by comparison with GSTM1-positive genotype (2.05 +/- 1.30 vs. 1.66 +/- 1.39 adducts/10(8) nucleotides; P = .018). This finding is more pronounced in the Teplice district (2.33 +/- 1.36 vs. 1.88 +/- 1.56 adducts/10(8) nucleotides; P = .053) than for the Prachatice district (1.61 +/- 1.09 vs. 1.36 +/- 1.10 adducts/10(8) nucleotides; P = .248) and for nonsmokers (1.45 +/- 0.82 vs. 1.18 +/- 0.93 adducts/10(8) nucleotides; P = .029) more than for smokers (3.45 +/- 1.14 vs. 2.95 +/- 1.62 adducts/10(8) nucleotides; P = .085). Significant district and seasonal differences were found in subgroups with GSTM1-negative genotype. DNA adduct levels in placentas of the GSTM1-negative subgroup were higher in mothers living in the polluted district of Teplice than in Prachatice (P = .012). The adduct levels in placentas sampled in the summer period were higher than in the winter period in the GSTM1-negative population (P = .006). No effect of the NAT2 genotype on DNA adduct levels was observed.
authors.affiliation: Laboratory of Genetic Ecotoxicology, Regional Institute of Hygiene of Central Bohemia, Prague, Czech Republic.
authors.forename: J
authors.initials: J
authors.lastname: Topinka
authors.forename: B
authors.initials: B
authors.lastname: Binková
authors.forename: G
authors.initials: G
authors.lastname: Mracková
authors.forename: Z
authors.initials: Z
authors.lastname: Stávková
authors.forename: V
authors.initials: V
authors.lastname: Peterka
authors.forename: I
authors.initials: I
authors.lastname: Benes
authors.forename: J
authors.initials: J
authors.lastname: Dejmek
authors.forename: J
authors.initials: J
authors.lastname: Lenícek
authors.forename: T
authors.initials: T
authors.lastname: Pilcík
authors.forename: R J
authors.initials: RJ
authors.lastname: Srám
mesh_terms: D000293:Adolescent; D000328:Adult; D000393:Air Pollutants / Q000633:toxicity*; D001191:Arylamine N-Acetyltransferase / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D001205:Ascorbic Acid / Q000097:blood; D018153:Czech Republic; D018736:DNA Adducts / Q000187:drug effects / Q000235:genetics*; D005260:Female; D005312:Fetal Blood / Q000378:metabolism; D005982:Glutathione Transferase / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D010920:Placenta / Q000187:drug effects* / Q000378:metabolism; D011084:Polycyclic Aromatic Hydrocarbons / Q000032:analysis / Q000633:toxicity; D011247:Pregnancy; D012424:Rural Population; D012907:Smoking; D014505:Urban Population; D014801:Vitamin A / Q000097:blood; D014810:Vitamin E / Q000097:blood
chemical_list: D000393:Air Pollutants; D018736:DNA Adducts; D011084:Polycyclic Aromatic Hydrocarbons; D014801:Vitamin A; D014810:Vitamin E; D001191:Arylamine N-Acetyltransferase; D005982:Glutathione Transferase; D001205:Ascorbic Acid