Biomarkers in Maternal and Newborn Blood Indicate Heightened Fetal Susceptibility to Procarcinogenic DNA Damage

Abstract

Polycyclic aromatic hydrocarbons (PAHs) such as benzo[a]pyrene (BaP) are widespread air contaminants released by transportation vehicles, power generation, and other combustion sources. Experimental evidence indicates that the developing fetus is more susceptible than the adult to carcinogenic effects of PAHs, although laboratory studies in rodents suggest that the dose to fetal tissues is an order of magnitude lower than that to maternal tissues. To assess fetal versus adult susceptibility to PAHs and environmental tobacco smoke (ETS), we compared carcinogen-DNA adducts (a biomarker associated with increased cancer risk) and cotinine (a biomarker of tobacco smoke exposure) in paired blood samples collected from mothers and newborns in New York City. We enrolled 265 nonsmoker African-American and Latina mother–newborn pairs in New York City between 1997 and 2001 (estimated average ambient air BaP concentrations < 0.5 ng/m3). Despite the estimated 10-fold lower fetal dose, mean levels of BaP-DNA adducts as determined by high-performance liquid chromatography–fluorescence were comparable in paired New York City newborn and maternal samples (0.24 adducts per 108 nucleotides, 45% of newborns with detectable adducts vs. 0.22 per 108 nucleotides, 41% of mothers with detectable adducts). However, by the Wilcoxon signed-rank test, the levels in newborns were higher (p = 0.02). Mean cotinine was higher in newborns than in mothers (1.7 ng/mL, 47% detectable vs. 1.28 ng/mL, 44% detectable). Consistent with our prior study in a Caucasian Polish population, these results indicate increased susceptibility of the fetus to DNA damage and reduced ability to clear ETS constituents. The findings have implications for risk assessment, given the need to protect children as a sensitive subset of the population.

Treatment of Pregnant Women with a Betamimetic and Verapamil Increases the Micronuclei Frequency in Umbilical Cord Blood Lymphocytes

“…One of the reasons is that the placenta does not completely protect the fetus from the outside influences (Vähäkangas and Myllynen 2006;Myren et al 2007). Factors that may increase fetal susceptibility include higher rates of cell proliferation, the greater number of target cells at risk, lower immunologic competence, and decreased capacity to activate and detoxify carcinogens as well as to repair DNA (Anderson et al 2000;Perera et al 2004;Whyatt et al 2004). A great number of authors showed that the frequency of damages in genetic material of neonates and children, such as MN and chromosome aberrations, increased with the concentration of environmental agents (Bocskay et al 2005;Milošević-Djordjević et al 2005, 2007bNeri et al 2006).…”

Prenatal Exposure to Air Pollution, Maternal Psychological Distress, and Child Behavior

“…[2][3][4][5][6] Socioeconomic and psychosocial factors, including poverty, maternal education, and maternal psychological distress, are important determinants of fetal and child development. [6][7][8][9][10][11][12][13][14][15][16][17] In addition, prenatal maternal stress and maternal psychological distress, reflective of maternal affective or emotional functioning, have also been associated with child behavioral development.…”

Environmental tobacco smoke and sudden infant death syndrome: a review

“…Additionally, they illustrate the biologic capacity of nicotine and cotinine to concentrate in the fetus, as suggested in the model by Gentry et al (2003). In five studies, higher biomarker levels were detected in fetal/neonatal samples than in maternal samples (Luck et al, 1985;Nafstad et al, 1995;Jauniaux et al, 1999;Whyatt et al, 2001;Perera et al, 2004).…”

“…Of the eight studies to be described, five studied populations of both active smokers and non-smoking mothers exposed to ETS (Eliopoulos et al, 1994;Nafstad et al, 1995;Jauniaux et al, 1999;Klein and Koren, 1999;Whyatt et al, 2001;Perera et al, 2004). The remaining studies included only active smokers and non-ETS exposed non-smokers in their analyses (Luck et al, 1985;Donnenfeld et al, 1993;Mercelina-Roumans et al, 1996), but are worthy of discussion because of the added value they bring to understanding exposure to nicotine in the maternal/fetal system.…”

“…Environmental tobacco smoke is a major source of indoor air pollution, as indicated by recent data from the National Health and Nutrition Examination Survey (NHANES) (1999)(2000)(2001)(2002): the metabolite of nicotine, cotinine, was detected in serum samples among 50% of a stratified sample of nonsmokers in the United States (detection limit 5 0.05 ng/ml) (Centers for Disease Control and Prevention, 2005), suggesting that a high proportion of nonsmokers are exposed to ETS. Similarly, analysis of umbilical cord blood, placental tissue, urine, and other biologic specimens indicates fetal and neonatal exposure to nicotine via environmental tobacco smoke through the detection of cotinine (Ostrea et al, 1994;Dwyer et al, 1999;Jauniaux et al, 1999;Whyatt et al, 2001;Perera et al, 2004). Because legislation has restricted cigarette smoking in many workplaces and public areas, tobacco smoking inside the home is generally the most important source of ETS exposure, particularly for children (Jarvis et al, 2000).…”