Biomarkers of polycyclic aromatic hydrocarbon-DNA damage and cigarette smoke exposures in paired maternal and newborn blood samples as a measure of differential susceptibility

Human and experimental evidence indicates that the developing fetus may be more susceptible than the adult to the effects of certain carcinogens, incl uding some polycyclic aromatic hydrocarbons (PAHs), Factors that can modula te susceptibility include proliferation rates, detoxification capabilities, and DNA repair capacity. Biomarkers can facilitate quantification of age-r elated susceptibility among human populations. In this study, we report on three biomarkers measured in paired blood samples collected at birth from 1 60 Polish mothers and newborns: 70 pairs from Krakow (a city with high air pollution including PAHs) and 90 pairs from Limanowa (an area with lower am bient pollution but greater indoor coal use). Biomarkers were: WBC aromatic -DNA adducts by P-32-postlabeling and PAH-DNA adducts by ELISA (as indicato rs of DNA damage from PAHs and other aromatics) and plasma cotinine (as an internal dosimeter of cigarette smoke). Correlations were assessed by Spear man's rank test, and differences in biomarker levels were assessed by the W ilcoxon signed-ranks test. A significant correlation between paired newborn /maternal samples was seen for aromatic-DNA adduct levels (r 0.3; P < 0.001 ) and plasma cotinine (r = 0.8; P < 0.001) but not PAH-DNA adduct levels (r = 0.14; P = 0.13). Among the total cohort, levels of the three biomarkers were higher in newborn samples compared with paired maternal samples. The d ifference was significant for aromatic-DNA adduct levels (16.6 +/- 12.5 ver sus 14.21 +/- 15.4/10(8) nucleotides; P = 0.002) and plasma cotinine (14.2 +/- 35.5 versus 8.3 +/- 24.5 ng/ml; P < 0.001) but not for PAH-DNA adduct l evels (7.9 +/- 9.9 versus 5.9 +/- 8.2/ 10(8) nucleotides; P = 0.13). When a nalyses were restricted to the 80 mother/newborn pairs from whom the blood sample was drawn concurrently (within 1 h of each other), levels of all of the three biomarkers were significantly higher in the newborn compared with paired maternal blood samples (P < 0.05). Results suggest reduced detoxifi cation capabilities and increased susceptibility of the fetus to DNA damage , especially in light of experimental evidence that transplacental exposure s to PAHs are 10-fold lower than paired maternal exposures. The results hav e implications for risk assessment, which currently does not adequately acc ount for sensitive subsets of the population.