Transplacental transfer of environmental genotoxins--polycyclic aromatic hydrocarbon-albumin in nonsmoking women.

Abstract

Transplacental transfer of genotoxic material has been determined by measuring the polycyclic aromatic hydrocarbon-albumin adduct level in serum isolated from the mother and the umbilical cord blood using a competitive enzyme-linked immunoadsorbent assay (ELISA) and the antibody (8E11( against benzo[a]pyrene (B[a]P) tetrols. Smoking women (median = 5.54 fmol B[a]P eq/micrograms albumin; n = 21 cases) and nonsmoking women living in rural areas (median = 4.99; n = 30) had higher adduct levels than nonsmoking women living in suburbia (median = 4.09; n = 37), whereas nonsmoking women living in the city of Aarhus had an intermediate level (median = 4.82; n = 40). The median adduct level in umbilical cord blood was significantly lower than in maternal blood, the maternal/fetal ratio being approximately 1.3. A positive association between the adduct levels in the mother and umbilical cord blood was observed. This study indicates that the competitive ELISA to detect B[a]P bound to serum albumin is sensitive enough to detect differences in the burden of genotoxic compounds in nonoccupationally exposed individuals. The lower adduct level in people living in suburbia suggests that local production of incomplete combustion products, like vehicle exhaust or heat generation, is a contributing factor to genotoxic compounds in the general environment.

Monitoring human exposure to 2-hydroxyethylating carcinogens.

“…However, in the present study, the GSTMI genotype did not seem to be related to HEV adduct levels at low exposure situations, although it is possible that it may have a slight effect at high exposures (e.g., cigarette smoking). A similar observation was made for the PAH-albumin levels (20).…”

“…More than half of the hemoglobin of the newborn is hemoglobin F, whose N-terminal valine content is only 50% of that of adult hemoglobin; therefore, a lower adduct level would be expected in the newborn. In contrast to the 2.5-to 2.7-fold ratio for adult:fetal adduct levels of HEV, the PAH-albumin adduct level was only 1.3 times greater in smoking mothers' blood compared to that in the umbilical cord blood (20). Glutathione transferase is directly involved in the conjugation and consequent detoxification of a variety of epoxides; it has been postulated that populations deficient in GSTMI activity may be at a potential higher risk of genotoxicity when exposed to these epoxides (21).…”

“…Of particular interest was the observation that rural dwellers had higher adduct levels than suburban dwellers, despite the fact that we had previously shown that exposure to exhaust -fumes positively contributes to HEV levels. 200 250 A similar observation was made for the polycyclic aromatic hydrocarbon (PAH)-albumin adduct, which was measured using (2-hydroxy-a competitive enzyme-linked immunoadnal and cord sorbent assay (ELISA) technique in the same population (20 Figure 3. Effect of area of residence on N-(2-hydroxyethyl)valine (HEV) adduct levels in nonsmokers' globin.…”

Monitoring Human Exposure to 2-Hydroxyethylating Carcinogens

“…More than half of the hemoglobin of the newborn is hemoglobin F, whose N-terminal valine content is only 50% of that of adult hemoglobin; therefore, a lower adduct level would be expected in the newborn. In contrast to the 2.5-to 2.7-fold ratio for adult:fetal adduct levels of HEV, the PAH-albumin adduct level was only 1.3 times greater in smoking mothers' blood compared to that in the umbilical cord blood (20). Glutathione transferase is directly involved in the conjugation and consequent detoxification of a variety of epoxides; it has been postulated that populations deficient in GSTMI activity may be at a potential higher risk of genotoxicity when exposed to these epoxides (21).…”

Development of an isotope dilution liquid chromatography/tandem mass spectrometry detection method for DNA adducts of selected aromatic amines

“…If these adducts are not repaired they can cause base substitutions or deletions that can lead to cancer [4]. The effects include formation of DNA adducts and protein adducts, increased rates of sister chromatid exchanges, lung, bladder and skin cancer, transplacental transfer, premature ovarian failure, and activation of the aromatic hydrocarbon receptors (AhR) [7][8][9][10][11][12][13][14]. Numerous publications have shown that the metabolic products of both 2-aminofluorene and benzidine are mutagenic [15][16][17][18][19][20][21].…”