Biomarkers in maternal and newborn blood indicate heightened fetal susceptibility to procarcinogenic DNA damage.
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).
Biomarkers are biochemical or molecular alterations that can document variation in susceptibility to carcinogens among human populations (Bearer 1998; Perera 2000; Whyatt et al. 2001). We have compared levels of biomarkers in paired maternal and newborn blood samples from a cohort of mothers and newborns in New York City. Biomarkers were BaP-DNA adducts in white blood cells (WBCs) measured by high-performance liquid chromatography (HPLC)-fluorescence and plasma cotinine (an internal dosimeter of cigarette smoke).
As an indicator of DNA damage, carcinogen-DNA adducts represent a critical step in the carcinogenic pathway and are an informative biomarker of age-related susceptibility and potential risk of cancer. The biologic basis for measuring DNA adducts derives from extensive experimental data supporting their role in the initiation and possibly in the progression of cancer (Perera 2000). An association between PAH-DNA adduct levels and cancer risk has been seen previously in both experimental and epidemiologic research (Bartsch and Hietanen 1996; Poirier and Beland 1992; Stowers and Anderson 1985; Tang et al. 1995, 2001; Veglia et al. 2003).
PAHs cross the placenta. However, experimental studies in laboratory animals using radiolabeled PAHs indicate that the dose to the fetus is generally at least an order of magnitude lower than the dose to paired maternal tissues (Neubert and Tapken 1988; Srivastava et al. 1986; Withey et al. 1993). In a number of rodent bioassays, fetal levels of PAH-DNA adducts have generally been higher than expected, given the lower estimated transplacental dose of PAHs (Lu et al. 1986; Lu and Wang 1990; Wang and Lu 1990). Similarly, levels of micronuclei formation and DNA single-strand breaks after transplacental PAH exposure have been shown experimentally to be higher in fetal than in paired maternal tissues (Bolognesi et al. 1985; Harper et al. 1989; Wang and Lu 1990). A previous study of a small number of maternal and cord blood samples from a Chinese population found comparable levels of PAH-DNA adducts measured by competitive enzyme-linked immunosorbent assay (ELISA) (Mumford et al. 1993).
Cotinine is the major proximal metabolite of nicotine but has a longer half-life in serum (15-40 hr vs. 1-3 hr for nicotine). Cotinine has been widely used as a specific marker of exposure to tobacco smoke (Benowitz 1996), which contains a myriad of carcinogens, including PAHs and the nicotine-derived carcinogens 4-(methylnitrosamino)- 1-(3-pyridyl)-1-butanone (NNK) and N'-nitrosonornicotine (Brunnemann et al. 1996; Hoffmann et al. 1985; U.S. Public Health Service 1990). Like nicotine, cotinine readily crosses the placenta (Haddow et al. 1988; Lambers and Clark 1996; Sorsa and Husgafvel-Pursiainen 1988; Ueda et al. 1989). The few studies comparing cotinine levels in paired maternal-fetal samples have given conflicting results (Donnenfeld et al. 1993; Jauniaux et al. 1999; Luck et al. 1985; Mercelina-Roumans et al. 1996; Nafstad et al. 1995).
We previously reported a detailed comparison of maternal-fetal biomarkers in a cohort of 320 mothers and newborns, including 70 mother-newborn pairs from Krakow, Poland (an industrial city with elevated ambient air pollution, including PAHs from coal burned for industrial purposes and residential heating) and 90 mother-newborn pairs from Limanowa, Poland (a town located 70 km southeast of Krakow with lower ambient pollution levels but 2-fold more frequent use of coal stoves for indoor home heating) (Whyatt et al. 2001). That study reported that PAH-DNA adducts measured by immunoassay were comparable in mothers and their newborns and that PAH-aromatic adducts measured by 32p-postlabeling were significantly higher in newborns than in mothers (Whyatt et al. 2001). Here we present results of analysis of biomarkers in 530 New York City mothers and newborns (265 pairs). The two populations (U.S. and Polish) represent an estimated 10- to 30-fold range of exposure to PAHs.
Materials and Methods
Study populations and biomarkers. Study subjects are nonsmoking Dominican and African-American women residing in Washington Heights, Central Harlem, and the South Bronx, New York, who delivered at New York Presbyterian Medical Center, Harlem Hospital, or their satellite clinics since February 1998, as previously described (Perera et al. 2003) (Table 1). Subjects signed a consent form approved by the Columbia University institutional review board. Race/ethnicity was self-identified. Subjects were interviewed using a questionnaire to elicit environmental and health histories, including exposure to tobacco smoke at home or work and dietary ingestion of PAHs via smoked, fried, broiled, barbecued, and grilled foods. Subjects included in the present analysis are those with available PAH-DNA adduct data for both mother and child. Not all subjects in the ongoing parent study (n = 474) had adduct data available because assays are ongoing and in some cases the amount of DNA was inadequate for analysis. However, the present subset is representative of the larger study cohort in that there were no significant differences between the present subset and the overall cohort with respect to any of the demographic and exposure variables shown in Table 1. Maternal blood (30-35 mL) was collected within 1 day postpartum, and umbilical cord blood (30-60 mL) was collected at delivery (Perera et al. 2003). Samples were transported to the laboratory immediately after collection. The huffy coat, packed red blood cells, and plasma were separated and stored at -70[degrees]C. BaP-DNA adducts in extracted WBC DNA were analyzed using the HPLC-fluorescence method of Alexandrov et al. (1992), which detects BaP tetraols. The assay gives zero values when unexposed calf thymus DNA is tested (D. Tang, personal communication). The method has a coefficient of variation of 12% and a lower limit of detection of 0.25 adducts per 10s nucleotides. HPLC analysis of DNA samples for BaP-DNA adducts was performed in batches, with 18-paired maternal and newborn samples in the same batch. A portion of each sample was shipped to the Centers for Disease Control and Prevention for analysis of cotinine using HPLC atmospheric-pressure ionization tandem mass spectrometry, as previously described (Bernert et al. 2000). Current data on annual average ambient concentrations of BaP in New York City are not available. However, outdoor 24-hr average BaP concentrations measured in U.S. urban areas have generally been in the range of 0.5-4 ng/[m.sup.3] in recent years (U.S. EPA 1990). Personal air monitoring of the New York City mothers for 48 hr during pregnancy provided data on PAHs, including BaP (Perera et al. 2003). For the first 344 subjects analyzed, the average personal BaP concentration was 0.5 ng/[m.sup.3] (range, 0.02-6.44). This may be an overestimate of mean ambient exposure because personal monitoring can also reflect indoor sources such as ETS. We estimate that the ambient BaP exposure of the New York City cohort, and by inference their exposure to other related PAHs, was at least 6- to 30-fold lower than that of the Polish cohort (0.5 vs. 3-15 ng/[m.sup.3]).
Statistical analyses. Statistical analyses used nonparametric methods because of the distributional properties of the biomarkers and because many of the samples were below the limit of detection. As in prior studies (Whyatt et al. 2001), we assigned nondetectable samples a value midway between the limit of detection and zero. We used nonparametric methods because the variables were not normally distributed. Spearman's rank test was used to test correlations between biomarkers in paired maternal and newborn samples, whereas differences between biomarker levels in paired maternal versus newborn samples were assessed by the Wilcoxon signed-rank test. The variable for ETS exposure was based on the presence of smoker(s) in the home, and that for dietary PAHs on frequency of consumption of fried, broiled, or barbecued food. Associations were considered significant at p [less than or equal to] 0.05.
The demographic characteristics of the 265 mother-newborn pairs from the New York City cohort study are provided in Table 1. The mothers were all nonsmokers. Detectable adduct levels were found in 42% of mothers and 45% of newborns. Detectable adducts were found in 53 (34%) newborns whose mothers had nondetectable levels of adducts; 43 (30%) mothers with detectable adducts had newborns with nondetectable levels of adducts (see Table 2). Levels of adducts in paired newborn-maternal samples were modestly but significantly correlated (r = 0.28, p < 0.001), as were cotinine levels (r = 0.31, p < 0.001). DNA adducts were not significantly correlated with cotinine in either maternal (r = 0.07, p = 0.36) or newborn (r = 0.05, p = 0.54) samples. ETS was significantly correlated with cotinine in both maternal (r= 0.4,p < 0.001) and newborn (r= 0.4, p < 0.001) samples. Dietary PAHs and ETS were not significantly associated with adducts (p > 0.05), nor were adducts correlated with PAHs in air monitored during pregnancy (mothers: r= 0.01,p = 0.9; newborns: r= 0.02, p = 0.8). Mean cotinine levels in mothers and newborns were higher in African Americans than in Dominicans, as was ETS exposure (p < 0.05). However, mean adduct levels did not differ between the two ethnic groups.
As shown in Table 3, the mean levels of BaP-DNA adducts (per 108 nucleotides) were comparable in New York City newborns and mothers (0.24, 45% detectable in newborns vs. 0.22, 41% detectable in mothers). However, by the Wilcoxon signed-rank test, the concentrations in newborns were significantly higher than those in the mothers (p = 0.02).
Cotinine levels were significantly higher in newborns (1.7 per [10.sup.8] nucleotides, 47% detectable vs. 1.28 per [10.sup.8] nucleotides, 44% detectable; p < 0.001). Table 4 provides details on the cotinine data.
In a cohort of mothers and newborns from an inner-city minority population in New York City, given the lower estimated dose of PAHs to the fetus, the levels of DNA damage from PAHs in WBC were higher than expected in newborns compared with paired mothers. The results are consistent with our prior finding in a Polish cohort of 160 paired Caucasian mothers and newborns (Whyatt et al. 2001) that PAH-DNA adducts measured by ELISA and PAH-aromatic adducts measured by [sup.32]P-postlabeling were significantly higher in the newborns. Although the methods of adduct analysis differed between the two studies, they all reflect DNA damage from PAHs and related aromatic compounds. Comparing the three assays with respect to specificity to exposure, the postlabeling method detects the broadest spectrum of adducts (multiple PAHs and other aromatic/hydrophobic compounds bound to DNA); the ELISA detects BaP diol-epoxide (DE)-DNA adducts and structurally related PAH-DNA adducts; and the HPLC-fluorescence method is the most specific (BaP-DNA only). The results point to increased susceptibility of the developing fetus to DNA damage from this class of carcinogens. The lack of a correlation between adducts and ETS, monitored PAHs in air, or dietary PAHs probably reflects the fact that adducts capture both individual exposure and susceptibility.
There are no data in humans on maternal versus fetal dose of PAHs. However, experimental studies in rodents using radiolabeled PAHs indicate that the dose to the embryo/ fetus is generally an order of magnitude or more lower than the dose to paired maternal tissues (Neubert and Tapken 1988; Srivastava et al. 1986; Withey et al. 1993; reviewed in Whyatt et al. 2001). Because humans and rodents may not metabolize PAHs in the same way, the data suggest, but do not prove, that the human fetus also has differential exposure. With this caveat, our findings suggest that the amount of DNA damage per unit dose of PAHs may be on the order of 10-fold higher in the fetus relative to the mother. Increased susceptibility could result from reduced detoxification capabilities or decreased DNA repair capacity during fetal development and may be an important factor in the observed greater carcinogenic impact of PAHs when administered to experimental animals prenatally or neonatally compared with later in life (Rice and Ward 1982; Soyka 1980; Tothet al. 1963; Vesselinovitch et al. 1975; Waiters 1966).
Against the backdrop of the Polish study, our present finding indicates heightened susceptibility of the fetus to PAH-DNA damage over a wide range of BaP exposure (30-fold range, from 0.5 to 15 ng/[m.sup.3]). This is of concern in light of the association seen previously in molecular epidemiologic research between PAH-DNA adduct levels and cancer risk (Tang et al. 2001). In a prior study of Polish newborns, an association has also been observed between PAH-DNA adducts in cord blood and adverse birth outcomes (Perera et al. 1998).
In the New York City cohort, as in the Polish cohort, cotinine levels were significantly higher in newborn plasma compared with paired maternal plasma. Few prior studies have compared cotinine levels in mother-newborn pairs and results have been conflicting (Donnenfeld et al. 1993; Jauniaux et al. 1999; Luck et al. 1985; Mercelina-Roumans et al. 1996; Nafstad et al. 1995). Our present results in nonsmoking mothers and newborns suggest that, like nicotine, cotinine concentrates in the fetus (Lambers and Clark 1996; Luck et al. 1985). However, some of the differences we observed between fetal and maternal samples may have occurred because the maternal blood samples were collected on the day after delivery, whereas the newborn samples were collected at delivery. We note, however, that among 80 Polish mother and newborn pairs whose blood samples were collected within 1 hr of each other the cotinine was significantly higher in the newborns (p < 0.05) (Whyatt et al. 2001). Cotinine has low toxicity relative to nicotine (Jordanov 1990; Lambers and Clark 1996) but is a good internal dosimeter for nicotine (Benowitz 1996). Concentration of nicotine and cotinine in the fetus appears to be caused by reduced clearance during fetal development and by the fact that, in addition to transfer from the maternal circulation, the fetus is exposed from gastrointestinal reabsorption of the chemicals in swallowed amniotic fluid (Jauniaux et al. 1999). The adverse effects of nicotine on fetal growth are well documented (Lambers and Clark 1996). In addition, like BaP, the nicotine-derived nitrosamine NNK binds to DNA to form adducts (Hecht 1999) and is a potent transplacental carcinogen in experimental bioassays (Jordanov 1990).
These findings highlight the need for pollution and smoking prevention programs to protect women of childbearing age and their children from PAHs and ETS. Individuals are generally exposed throughout most of their life to low levels of carcinogens; if, in addition, they experience prenatal exposure to carcinogens, the possibility that they will develop cancer over their lifetime may be disproportionately increased (Bulay and Wattenberg 1971). There are several possible factors involved. First, as shown in our research, prenatal exposures apparently result in differentially higher levels of procarcinogenic DNA damage. Second, there is a higher probability that low-level/long-latency effects will be manifested as cancer during the individual's life span if these effects are initiated in utero rather than later in life. Therefore, the results presented here have implications for risk assessment and environmental health policy and highlight the need to protect pregnant women and especially their children as a sensitive subset of the population.
Consistent with a prior study in a Caucasian Polish population, these results in a New York City minority population 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.
Alexandrov K, Rojas M, Geneste O, Castegnaro M, Camus AM, Pesruzzelli S, et al. 1992. An improved fluorometric assay for dosimetry of benzo(a)pyrene diol-epoxide-DNA adducts in smokers' lung: comparisons with total bulky adducts and aryl hydrocarbon hydroxylase activity. Cancer Res 52:6248-6253.
Anderson LM, Diwan BA, Fear NT, Roman E. 2000. Critical windows of exposure for children's health: cancer in human epidemiological studies and neoplasms in experimental animal models. Environ Health Perspect 108:573-594.
Bartsch H, Hietanen E. 1996. The role of individual susceptibility in cancer burden related to environmental exposure. Environ Health Perspect 104:569-577.
Bearer CF. 1998. Biomarkers in pediatric environmental health: a cross-cutting issue. Environ Health Perspect 106:813-816.
Benowitz NL. 1996. Cotinine as a biomarker of environmental tobacco smoke exposure. Epidemiol Rev 18:188-204.
Bernert JT, McGuffey JE, Morrison MA, Pirkle JL. 2000. Comparison of serum and salivary cotinine measurements by a sensitive high-performance liquid chromatography-tandem mass spectrometry method as an indicator of exposure to tobacco smoke among smokers and nonsmokers. J Anal Toxicol 24:333-339.
Bolognesi C, Rossi L, Barbieri 0, Santi L. 1985. Benzo[a]pyrene-induced DNA damage in mouse fetal tissues. Carcinogenesis 6:1091-1095.
Brunnemann KD, Prokopczyk B, Djordjevic MV, Hoffmann D. 1996. Formation and analysis of tobacco-specific N-nitrosamines. Crit Rev Toxicol 28:121-137.
Bulay OM, Wattenberg LW. 1971. Carcinogenic effects of polycyclic hydrocarbocarcinogens administrated to mice during pregnancy on the progeny. J Natl Cancer Inst 46:397-402.
Donnenfeld AE, Pulkkinen A, Palomaki BE, Knight GJ, Haddow JE. 1993. Simultaneous fetal and maternal cotinine levels in pregnant women smokers. Am J Obstet Gynecol 168:781-782.
Fraumeni JF Jr. 1974. The susceptibility of the fetus and child to chemical pollutants. Chemicals in human teratogenesis and transplacental carcinogenesis. Pediatrics 53:807-812.
Haddow JE, Knight GJ, Palomaki GE, McCarthy JE. 1988. Second-trimester serum cotinine levels in nonsmokers in relation to birth weight. Am J Obstet Gynecol 159:481-484.
Harper BL, Ramanujam VM, Legator MS. 1989. Micronucleus formation by benzene, cyclophesphamide, benzo(e)pyrene, and benzidine in male, female, pregnant female and fetal mice. Teratog Carcinog Mutagen 9:239-252.
Hecht SS. 1999. DNA adduct formation from tobacco-specific N-nitrosamines. Mutat Res 424:127-142.
Hoffmann O, Lavoie EJ, Hecht SS. 1985. Nicotine: a precursor for carcinogens. Cancer Lett 26:67-75.
IARC. 1983. Approaches to Classifying Chemical Carcinogens according to Mechanisms to Actions. IARC Technical Report no. 53/001. Lyon, France: International Agency for Research on Cancer.
Jauniaux E, Gulbis B, Acharya G, Thiry P, Rodeck C. 1999. Maternal tobacco exposure and cotinine levels in fetal fluids in the first half of pregnancy. Obstet Gynecol 93:25-29.
Jordanov JS. 1990. Cotinine concentrations in amniotic fluid and urine of smoking, passive smoking and non-smoking pregnant women at term and in the urine of their neonates on 1st day of life. Eur J Pediatr 149:734-737.
Lambers GS, Clark KE. 1996. The maternal and fetal physiologic effects of nicotine. Sernin Perinatol 20:115-126.
Lewtas J. 1994. Human exposure to complex mixtures of air pollutants. Toxicol Lett 72:163-169.
Lu LJ, Disher RM, Reddy MV, Randerath K. 1986. [sup.32]P-postlabeling assay in mice of transplacental DNA damage induced by the environmental carcinogens safrole, 4-aminobiphenyl and benzo(a)pyrene. Cancer Res 46:3046-3054.
Lu LJ, Wang MY. 1990. Modulation of benzo(a)pyrene-induced covalent DNA modification in adult and fetal mouse tissues by gestation stage. Carcinogenesis 11:1367-1372.
Luck W, Nau H, Hansen R, Steldenger R. 1985. Extent of nicotine and cotinine transfer to the human fetus, placenta and amniotic fluid of smoking mothers. Dev Pharmacol Ther 8:384-395.
Mercelina-Roumans PE, Schouten H, Ubachs JM, van Wersch JW. 1996. Cotinine concentrations in plasma of smoking pregnant women. Eur J Clin Chem Clin Riochem 34:525-528.
Mumford JL, Lee X, Lewtas J, Young TL, Santella RM. 1993. DNA adducts as biomarkers for assessing exposure to polycyclic aromatic hydrocarbons in tissues from Xuan Wei women with high exposure to coal combustion emissions and high lung cancer mortality. Environ Health Perspect 99:83-87.
Nafstad P, Magnus P, Stray-Pedersen B. 1995. Opposing placental gradients for thiocyanate and cotinine at birth. Early Hum Dev 42:73-79.
National Research Council. 1993. Pesticides in the Diets of Infants and Children. Washington, DC:National Academy Press.
Neubert D, Tapken S. 1980. Transfer of benzo(a)pyrene into mouse embryos and fetuses. Arch Toxicol 62:236-239.
Perera FP. 2000. Molecular epidemiology: on the path to prevention? J Natl Cancer Inst 92:602-612.
Perera FP, Rauh V, Tsai WY, Kinney P, Camann D, Barr D, et al. 2003. Effects of transplacental exposure to environmental pollutants on birth outcomes in a multiethnic population. Environ Health Perspect 111:201-205.
Perera FP, Whyatt RM, Jedrychowski W, Rauh V, Manchester D, Santella RM, et al. 1998. Recent developments in molecular epidemiology: a study of the effects of environmental polycylic aromatic hydrocarbons on birth outcomes in Poland. Am J Epidemiol 147:309-314.
Poirier MC, Beland FA. 1992. DNA adduct measurements and tumor incidence during chronic carcinogen exposure in animal models: implications for DNA adduct-based human cancer risk assessment. Chem Res Toxicol 5:749-755.
Rice JM, Ward JM. 1982. Age dependence of susceptibility to carcinogenesis in the nervous system. Ann NY Acad Sci 381:274-289.
Sorsa M, Husgafvel-Pursiainen K. 1988. Assessment of passive and transplacental exposure to tobacco smoke. IARC Sci Publ 89:129-132.
Soyka LF. 1980. Hepatic drug metabolizing enzyme activity and tumorigenesis in mice following perinatal exposure to benzo(a)pyrene. Pediatr Pharmacol 1:85-96.
Srivastava VK, Chauhan SS, Srivastava PK, Kumar V, Misra UK. 1986. Fetal translocation and metabolism of PAH obtained from coal fly ash given intratracheally to pregnant rats. J Toxicol Environ Health 18:459-469.
Stowers SJ, Anderson MW. 1985. Formation and persistence of benzo[a]pyrene metabolite-DNA adducts. Environ Health Perspect 62:31-39.
Tang D, Phillips DH, Stampfer M, Mooney LA, Hsu Y, Cho S, et al. 2001. Association between carcinogen-DNA adducts in white blood cells and lung cancer risk in the physicians health study. Cancer Res 61:6708-6712.
Tang D, Santella RM, Blackwood A, Young TL, Mayer J, Jaretzki A, et al. 1995. A molecular epidemiological case-control study of lung cancer. Cancer Epidemiol Biomarkers Prey 4:341-346.
Toth B, Rappaport H, Shubik P. 1963. Influence of dose and age on the induction of malignant lymphomas and other tumors by 7,12-dimethylbenz[a]anthrocene in Swiss mice. J Natl Cancer Inst 30:723-741.
Ueda Y, Morikawa H, Funakoshi T, Kobayashi A, Yamasaki A, Takeuchi K, et al. 1989. Estimation of passive smoking during pregnancy by cotinine measurement and its effect on fetal growth. Nippon Sanka Fujinka Gakkai Zasshi/Acta Obstet Gynaecol Jpn 41:454-460.
U.S. EPA. 1990. Aerometric Information Retrieval System (AIRS), Data for 1985-1990. Research Triangle Park, NC:U.S. Environmental Protection Agency.
U.S. Public Health Service, Office of the Surgeon General. 1990. The Health Benefits of Smoking Cessation: A Report of the Surgeon General. Washington, DC:U.S. Public Health Service, Office on Smoking and Health.
Veglia F, Matullo G, Vineis P. 2003. Bulky DNA adducts and risk of cancer: a meta-analysis. Cancer Epidemiol Biomarkers Prev 12:157-160
Vesselinovitch SC, Kyriazis AP, Mihailovich N, Rao KV. 1978. Conditions modifying development of tumors in mice at various sites by benzo(a)pyrene. Cancer Res 35:2948-2953.
Walters MA. 1966. The induction of lung tumours by the injection of 9,10-dimethyl-1,2-benzanthracene (DMBA) into newborn suckling and young adult mice. A dose response study. Br J Cancer 20:148-160.
Wang MY, Lu LJ. 1990. Differential effect of gestation stage on benzo(a)pyrene-induced micronucleus formation and/ or covalent DNA modifications in mice. Cancer Res 50:2146-2151.
Whyatt RM, Jedrychowski W, Hemminki K, Santella RM, Tsai VVY, Yang K, et aL 2001. Biomarkers of polycyclic aromatic hydrocarbon-DNA damage and cigarette smoke exposures in paired maternal and newborn blood samples as a measure of differential susceptibility. Cancer Epidemiol Biomarker Prey 10:581-588.
Withey JR, Shedden J, Law FC, Abedini S. 1993. Distribution of benzo[a]pyrene in pregnant rats following inhalation exposure and a comparison with similar data obtained with pyrene. J Appl Toxicol 13:193-202.
Frederica P. Perera, (1) Deliang Tang, (1) Yi-Hsuan Tu, (1) Linda Aft Cruz, (1) Mejico Borjas, (1) Tom Bernert, (2) and Robin M. Whyatt (1)
(1)Mailman School of Public Health of Columbia University, Department of Environmental Health Sciences, New York, New York, USA;
(2)Centers for Disease Control and Prevention, National Center for Environmental Health, Division of Laboratory Sciences, Atlanta, Georgia, USA
Address correspondence to F.P. Perera, Mailman School of Public Health of Columbia University, Department of Environmental Health Sciences, 60 Haven Ave., B-109, New York, NY 10032 USA. Telephone: (212) 304-7280. Fax: (212) 544-1943. E-mail: email@example.com
We acknowledge the assistance of J. Zhou for BaP-DNA adduct analysis, and the research staff, S.A. Lederman, A. Reyes, D. Diaz, J. Dietrich, J. Ramirez, Y. Cosme, and D. Holmes.
This work was supported by grants from the National Institute of Environmental Health Sciences (5 P01 ES09600 and 5 RO1 ES08977), the U.S. Environmental Protection Agency (EPA R827027), the U.S. Department of Energy (DE FG02-93R61719), Irving General Clinical Research Center (RR00645), Bauman Family Foundation, Gladys and Roland Harriman Foundation, New York Community Trust, Educational Foundation of America, and the V. Kann Rasmussen Foundation.
The authors declare they have no competing financial interests.
Received 3 November 2003; accepted 22 March 2004.
Table 1. New York City cohort: number of mother--newborn pairs, (a) maternal age, race/ethnicity, and ETS exposure of mothers. Characteristics Values No. of mother-newborn pairs 265 Mother's age [years (mean [+ or -] SD)] 24.5 [+ or -] 4.8 Race/ethnicity [no. of pairs (%)] African American 102 (37.7) Dominican 163 (62.3) Self-reported ETS [no. of pairs (%)] ETS exposure 100 (37.7) No ETS exposure 165 (62.3) (a) Number of pairs with adduct data. Table 2. Adduct data for 265 mother-newborn pairs. Mothers' adduct levels Newborns' adduct levels Nondetectable Low detectable Nondetectable No. 103 25 Percent of newborns 70.5 17.1 Percent of mothers 66.0 53.2 Low detectable (a) No. 25 15 Percent of newborns 45.5 27.3 Percent of mothers 16.0 31.9 High detectable (a) No. 28 7 Percent of newborns 43.8 10.9 Percent of mothers 17.9 14.9 Total No. 156 47 Percent of newborns 58.9 17.7 Percent of mothers 100.0 100.0 Mothers' adduct levels Newborns' adduct levels High detectable Total Nondetectable No. 18 146 Percent of newborns 12.3 100.0 Percent of mothers 29.0 55.1 Low detectable (a) No. 15 55 Percent of newborns 27.3 100.0 Percent of mothers 24.2 20.8 High detectable (a) No. 29 64 Percent of newborns 45.3 100.0 Percent of mothers 46.8 24.2 Total No. 62 265 Percent of newborns 23.4 100.0 Percent of mothers 100.0 100.0 (a) The cut point of low/high detectable was the median of the detectable level of adducts for mothers and newborns, respectively. Table 3. New York City cohort: biomarkers in paired maternal and newborn blood samples. Mean [+ or -] SD (% detectable) Maternal WBC BaP-DNA adduct levels by HPLC-fluorescence (per [10.sup.8] nucleotides) Total cohort (265 pairs) 0.22 [+ or -] 0.14 (41) ETS exposure (100 pairs) 0.23 [+ or -] 0.16 (42) No ETS exposure (165 pairs) 0.21 [+ or -] 0.12 (41) Plasma cotinine (ng/mL) Total cohort (160 pairs) 1.28 [+ or -] 9.77 (44) ETS exposure (65 pairs) 3.04 [+ or -] 15.22 (69) No ETS exposure (95 pairs) 0.08 [+ or -] 0.24 (26) Mean [+ or -] SD (% detectable) Newborn WBC BaP-DNA adduct levels by HPLC-fluorescence (per [10.sup.8] nucleotides) Total cohort (265 pairs) 0.24 [+ or -] 0.15 (45) ETS exposure (100 pairs) 0.24 [+ or -] 0.15 (44) No ETS exposure (165 pairs) 0.24 [+ or -] 0.15 (45) Plasma cotinine (ng/mL) Total cohort (160 pairs) 1.7 [+ or -] 10.50 (47) ETS exposure (65 pairs) 4.02 [+ or -] 16.27 (69) No ETS exposure (95 pairs) 0.12 [+ or -] 0.48 (32) p-Value WBC BaP-DNA adduct levels by HPLC-fluorescence (per [10.sup.8] nucleotides) Total cohort (265 pairs) 0.02 (a) ETS exposure (100 pairs) 0.31 No ETS exposure (165 pairs) 0.08 Plasma cotinine (ng/mL) Total cohort (160 pairs) < 0.001 ETS exposure (65 pairs) < 0.001 No ETS exposure (95 pairs) 0.001 (a) Wilcoxon signed-rank test for paired samples comparing maternal and newborn levels. Table 4. Cotinine data for 160 mother--newborn pairs. Mothers' cotinine levels Newborns' cotinine level Nondetectable Low detectable Nondetectable No. 81 3 Percent of newborns 95.3 3.5 Percent of mothers 90.0 8.3 Low detectable (a) No. 9 26 Percent of newborns 24.3 70.3 Percent of mothers 10.0 72.2 High detectable (a) No. 0 7 Percent of newborns 0 18.4 Percent of mothers 0 19.4 Total No. 90 36 Percent of newborns 56.3 22.5 Percent of mothers 100.0 100.0 Mothers' cotinine levels Newborns' cotinine level High detectable Total Nondetectable No. 1 85 Percent of newborns 1.2 100.0 Percent of mothers 2.9 53.1 Low detectable (a) No. 2 37 Percent of newborns 5.4 100.0 Percent of mothers 5.9 23.1 High detectable (a) No. 31 38 Percent of newborns 81.6 100.0 Percent of mothers 91.2 23.8 Total No. 34 160 Percent of newborns 21.3 100.0 Percent of mothers 100.0 100.0 (a) The cut point of low/high detectable was the median of the detectable level of adducts for mothers and newborns, respectively.
|Printer friendly Cite/link Email Feedback|
|Title Annotation:||Children's Health|
|Author:||Whyatt, Robin M.|
|Publication:||Environmental Health Perspectives|
|Date:||Jul 1, 2004|
|Previous Article:||Prenatal insecticide exposures and birth weight and length among an urban minority cohort.|
|Next Article:||Center for Risk and Integrated Sciences.|