Academic journal article Environmental Health Perspectives

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

Academic journal article Environmental Health Perspectives

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

Article excerpt

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/[m.sup.3]). 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 [10.sup.8] nudeotides, 45% of newborns with detectable adducts vs. 0.22 per 10s nudeotides, 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 dear ETS constituents. The findings have implications for risk assessment, given the need to protect children as a sensitive subset of the population. Key words: cancer, DNA adducts, fetus, polycyclic aromatic hydrocarbons, susceptibility. doi:10.1289/ehp.6833 available via http://dx.doi.org/[Online 22 March 2004]

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As previously discussed (Whyatt et al. 2001), experimental and human evidence indicates that the developing fetus and neonate have heightened susceptibility to certain chemical carcinogens compared with the adult (reviewed in Anderson et al. 2000; National Research Council 1993). 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; National Research Council 1993).

Polycyclic aromatic hydrocarbons (PAHs) are widespread pollutants commonly found in ambient air, as well as workplace air, food, and drinking water [International Agency for Research on Cancer (IARC) 1983]. Incomplete combustion of organic material is the major source of PAHs. Airborne PAHs result mainly from combustion of fossil fuels, tobacco products, and other organic materials. Generally, emissions from motor vehicles and residential heating are the major source of PAHs in outdoor urban air, whereas environmental tobacco smoke (ETS) is a major indoor source (Donnenfeld et al. 1993; Lewtas 1994). A number of PAHs, of which benzo[a]pyrene (BaP) is a representative member, are transplacental carcinogens in experimental bioassays, producing tumors in the liver, lung, lymphatic tissues, and nervous system of the offspring (Bulay and Wattenberg 1971; Rice and Ward 1982; Vesselinovitch et al. 1975). Experimental animal studies have demonstrated that the fetus and infant are more susceptible to PAH-induced carcinogenesis than are adults (Rice and Ward 1982; Soyka 1980; Toth et al. 1963; Vesselinovitch et al. 1975; Walters 1966). No comparable human data are available on age-related susceptibility to PAH carcinogenesis (Anderson et al. 2000). However, epidemiologic studies have shown the human fetus to be more sensitive than the adult to the carcinogenic effects of drugs such as diethylstilbestrol (Fraumeni 1974). …

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