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Pheno-and genotyping of a placental detoxication system in ecologically unfavorable regions of Ukraine

Pheno-and genotyping of a placental detoxication system in ecologically unfavorable regions of Ukraine

Ukrains'kyi Biokhimichnyi Zhurnal 73(3): 126-134

During 1991-1993 period a study of detoxifying activity of the fetoplacental barrier and genotyping of the major detoxifying enzymes in it (CYP1A1 Ile462Val, GSTP1 Ile104Val, GSTM1 present/absent) was undertaken in different regions of Ukraine that were radioactively contaminated with summary effective equivalent annual expositional doses (SEEAED approximately 1.7 mSv (Group I) and 0.1-0.4 mSv (Group III), chemically polluted Zaporizzhia, monitored for ambient levels of benzo(a)pyrene (BP) (Group II) and Poltava that was judged as "clean" one (Group IV). Glutathione-S-transferase (GSTase) and glutathionereductase (GSSG-Rase) activities of cytosol and concentration of thiobarbituric acid reacting compounds (TBA-reactants) and reduced low-molecular weight thiols (rLMW thiols) were used as phenotype parameters. Cytosolic GSTase activities were nearly two times less in the samples from radioactively contaminated area (Group I, SEEAED approximately 1.7 mSv) and in chemically polluted area (Group II, mean BP level 12.3 ng/m3), compared with the groups III and IV. The highest level of TBA-reactants indicative of lipid peroxidation in response to radiation was observed in Group I, while the lowest level in Group IV. The level of rLMW thiols was 2.5-4 times more in Group II comparative with Groups I, III and IV. The frequency of the genotypes in all the investigated samples corresponds to that reported for Caucasians. For the combined exposure groups, individuals with the CYP1A1 (Ile462Val) genotype (n = 5) had significantly higher levels of GST, GSSG-R and TBA reacting compounds compared to individuals with the Ile462Ile genotype (n = 14 for TBA-reactants and n = 24--for GST and GSSG-R). Despite the challenge of small numbers of individuals, stratification by exposure group for Groups I, II and III indicated significantly higher GST levels in CYP1A1 (Ile462Val) variants from Groups II and III (n = 3) compared to the Ile462Ile variants (n = 17). The data demonstrate contributions by both exposure and genotype on the detoxification of radiation and chemical damage in the human placenta.

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Accession: 046973158

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PMID: 12035543

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