DNA-ADDUCTS IN HUMAN PLACENTA AS RELATED TO AIR-POLLUTION AND TO GSTM1 GENOTYPE

DNA adducts in human placenta have been studied in relation to metabol ic genotype for glutathione S-transferase M1 (GSTM1) in 98 mothers liv ing in two regions with a different annual average air pollution level s: Northern Bohemia - the district of Teplice as polluted industrial a rea (mines, brown coal power plants) and Southern Bohemia - the distri ct of Prachatice as agricultural area without heavy industry. Forty-ni ne placenta samples (25 from the Teplice district and 24 from the Prac hatice district) from non-smoking mothers with the date of delivery in the summer period and 49 placenta samples (25 from the Teplice distri ct and 24 from Prachatice district) from mothers with the date of deli very in the winter period were analysed. The total DNA adduct levels w ere calculated as the sum of adducts in the diagonal radioactive zone (DRZ) and one distinct spot outside of the DRZ (termed X), which was d etected in almost all placenta samples. We found total DNA adduct leve ls of 1.40 +/- 0.87 (0.04-3.65) and 1.04 +/- 0.63 (0.11-3.08) adducts per 10(8) nucleotides for the Teplice and Prachatice districts, respec tively. The significant difference between both districts in placental DNA adduct levels was found for the winter sampling period only (1.49 vs. 0.96 adducts per 10(8) nucleotides; p = 0.023). No seasonal varia tion was observed for DNA adduct levels in the overall population stud ied. A positive GSTM1 genotype was detected in 51 subjects, while GSTM 1-null genotype was found in 47 subjects. Higher DNA adduct levels wer e detected in a group with GSTM1-null genotype (p = 0.009). This findi ng seems more significant for subjects in the Teplice district (p = 0. 047) than for those in the Prachatice district (p = 0.092). Significan t district and seasonal differences were found in subgroups carrying t he GSTM1-null genotype. DNA adduct levels in placentas of mothers with GSTM1-null genotype living in the polluted district of Teplice were h igher than those in Prachatice (p = 0.050); also the adduct levels in placentas sampled in the summer period were higher than those sampled in the winter period (p = 0.011). Our results indicate that simultaneo us analysis of DNA adducts and metabolic genotypes could emphasize the use of DNA adduct measurements, particularly in the case of the envir onmental exposure when the total doses of genotoxic pollutants are ver y low.