Topinka J, Binková B, Mracková G, Stávková Z, Benes I, Dejmek J, Lenícek J, Srám R J
Laboratory of Genetic Ecotoxicology, Regional Institute of Hygiene of Central Bohemia, Czech Academy of Sciences, Prague, Czech Republic.
Mutat Res. 1997 Apr 24;390(1-2):59-68. doi: 10.1016/s0165-1218(96)00166-8.
DNA adducts in human placenta have been studied in relation to metabolic genotype for glutathione S-transferase M1 (GSTM1) in 98 mothers living in two regions with a different annual average air pollution levels: Northern Bohemia-the district of Teplice as polluted industrial area (mines, brown coal power plants) and Southern Bohemia-the district of Prachatice as agricultural area without heavy industry. Forty-nine placenta samples (25 from the Teplice district and 24 from the Prachatice district) from non-smoking mothers with the date of delivery in the summer period and 49 placenta samples (25 from the Teplice district and 24 from Prachatice district) from mothers with the date of delivery in the winter period were analysed. The total DNA adduct levels were calculated as the sum of adducts in the diagnoal radioactive zone (DRZ) and one distinct spot outside of the DRZ (termed X), which was detected in almost all placenta samples. We found total DNA adduct levels 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, respectively. 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 variation was observed for DNA adduct levels in the overall population studied. A positive GSTM1 genotype was detected in 51 subjects, while GSTM1-null genotype was found in 47 subjects. Higher DNA adduct levels were detected in a group with GSTM1-null genotype (p = 0.009). This finding seems more significant for subjects in the Teplice district (p = 0.047) than for those in the Prachatice district (p = 0.092). Significant district and seasonal differences were found in subgroups carrying the GSTM1-null genotype. DNA adduct levels in placentas of mothers with GSTM1-null genotype living in the polluted district of Teplice were higher 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 simultaneous analysis of DNA adducts and metabolic genotypes could emphasize the use of DNA adduct measurements, particularly in the case of the environmental exposure when the total doses of genotoxic pollutants are very low.
我们对98名居住在两个年平均空气污染水平不同地区的母亲的胎盘进行了研究，分析了谷胱甘肽S-转移酶M1（GSTM1）代谢基因型与DNA加合物之间的关系。这两个地区分别是：北波希米亚的特普利采区，为污染严重的工业区（煤矿、褐煤发电厂）；南波希米亚的普拉哈蒂采区，为无重工业的农业区。我们分析了49份来自非吸烟母亲的胎盘样本（25份来自特普利采区，24份来自普拉哈蒂采区），这些母亲的分娩日期在夏季；以及49份来自分娩日期在冬季的母亲的胎盘样本（25份来自特普利采区，24份来自普拉哈蒂采区）。总DNA加合物水平通过对角放射性区域（DRZ）中的加合物与DRZ外一个明显斑点（称为X）的加合物之和来计算，几乎在所有胎盘样本中都能检测到X。我们发现，特普利采区和普拉哈蒂采区每10⁸个核苷酸的总DNA加合物水平分别为1.40±0.87（0.04 - 3.65）和1.04±0.63（0.11 - 3.08）个加合物。仅在冬季采样期发现两个地区胎盘DNA加合物水平存在显著差异（每10⁸个核苷酸分别为1.49和0.96个加合物；p = 0.023）。在所研究的总体人群中，未观察到DNA加合物水平的季节性变化。51名受试者检测出GSTM1基因型为阳性，47名受试者检测出GSTM1基因缺失型。GSTM1基因缺失型组的DNA加合物水平更高（p = 0.009）。这一发现对于特普利采区的受试者（p = 0.047）似乎比对普拉哈蒂采区的受试者（p = 0.092）更显著。在携带GSTM1基因缺失型的亚组中发现了显著的地区和季节差异。生活在污染严重的特普利采区且GSTM1基因缺失型母亲的胎盘DNA加合物水平高于普拉哈蒂采区（p = 0.050）；同样，夏季采样的胎盘加合物水平高于冬季采样的胎盘（p = 0.011）。我们的结果表明，同时分析DNA加合物和代谢基因型可以突出DNA加合物测量的作用，特别是在遗传毒性污染物总剂量非常低的环境暴露情况下。
