Abstract:Maternal smoking while pregnant is a plausible risk factor for childhood cancers because many seem to initiate in utero and tobacco-specific carcinogens cross the placenta. Social desirability bias may affect maternal report of smoking in case-control studies and could explain inconsistently observed associations with offspring cancer. Detection of tobacco smoke biomarkers in dried blood spots (DBS), which are increasingly stored by newborn screening programs, may improve retrospective assessment of fetal toba… Show more
“…Biological markers of exposure assessment to environmental carcinogens in the developing fetus have been limited previously to studies that have examined either placental exposure to carcinogens after delivery or the obtaining of biological specimens from the neonate (29,(84)(85)(86)(87)(88)(89)(90)(91). The latter process of using biological markers relies heavily on the obtaining of either meconium samples from the neonate after delivery, or small amounts of urine for analysis (92)(93)(94)(95)(96)(97)(98)(99).…”
Previous studies from this laboratory have focused on the characterization of blood protein adducts formed in utero as a result of maternal smoking during pregnancy. These biological samples, obtained during the third trimester of pregnancy, at delivery, have clearly shown a correlation between maternal smoking histories and exposure of the fetus to tobacco smoke carcinogens, including 4-aminobiphenyl and benzo(a)pyrene. In the present study, we examined exposure of the fetus during the first trimester of pregnancy to various environmental carcinogens, particularly those found in tobacco smoke. Amniotic fluid samples were obtained from women undergoing routine amniocentesis between 16 and 20 weeks gestational age. Amniotic fluid, produced by the fetal lungs and kidneys, is an important part of pregnancy and fetal development and this fluid surrounds the fetus throughout pregnancy. In these studies, samples of amniotic fluid were obtained from nonsmokers as well as 0.5 pack per day smokers, 1.0 pack per day smokers, and greater than 2.0 pack per day smokers. Maternal smoking status was determined by questionnaire as well as assessment of amniotic fluid for 39 Downloaded by [University of Kent] at 15:01 07 December 2014 40 S. R. Myers et al.
cotinine via immunoassay. Amniotic fluid samples were extracted and analyzed for the presence of polycyclic aromatic hydrocarbons (PAHs). A clear correlation was found between levels of maternal smoking and PAHs in the amniotic fluid.Amniotic fluid 1-hydroxypyrene levels ranged from 1.54 ± 0.12 µg/L in nonsmokers to 11.72 ± 0.67 µg/L in women smoking greater than 2 pks/da, indicating approximately a 10X increase over nonsmokers. Similar results were found 3-hydroxybenzo(a)pyrene, 6-hydroxybenzo(a)pyrene, and 3,6-dihydroxybenzo(a)pyrene, metabolites of the carcinogen benzo(a)pyrene as well as with the 9-hydroxy and 9,10-dihydroxy metabolites of anthracene. The 5-hydroxymethyl metabolite of 5-methylchrysene was found to range in concentrations from 1.65 ± 0.11 µg/L in nonsmokers to 12.67 ± 0.79 µg/L in greater than 2 packs per day smokers.These results demonstrate that amniotic fluid can serve as a biological marker of exposure to tobacco related polycyclic aromatic hydrocarbons. Identification of potentially harmful compounds detected at an early stage of pregnancy may prevent subsequent exposures to the fetus and as a result decrease the risk of potential genotoxic as well as teratogenic events.
“…Biological markers of exposure assessment to environmental carcinogens in the developing fetus have been limited previously to studies that have examined either placental exposure to carcinogens after delivery or the obtaining of biological specimens from the neonate (29,(84)(85)(86)(87)(88)(89)(90)(91). The latter process of using biological markers relies heavily on the obtaining of either meconium samples from the neonate after delivery, or small amounts of urine for analysis (92)(93)(94)(95)(96)(97)(98)(99).…”
Previous studies from this laboratory have focused on the characterization of blood protein adducts formed in utero as a result of maternal smoking during pregnancy. These biological samples, obtained during the third trimester of pregnancy, at delivery, have clearly shown a correlation between maternal smoking histories and exposure of the fetus to tobacco smoke carcinogens, including 4-aminobiphenyl and benzo(a)pyrene. In the present study, we examined exposure of the fetus during the first trimester of pregnancy to various environmental carcinogens, particularly those found in tobacco smoke. Amniotic fluid samples were obtained from women undergoing routine amniocentesis between 16 and 20 weeks gestational age. Amniotic fluid, produced by the fetal lungs and kidneys, is an important part of pregnancy and fetal development and this fluid surrounds the fetus throughout pregnancy. In these studies, samples of amniotic fluid were obtained from nonsmokers as well as 0.5 pack per day smokers, 1.0 pack per day smokers, and greater than 2.0 pack per day smokers. Maternal smoking status was determined by questionnaire as well as assessment of amniotic fluid for 39 Downloaded by [University of Kent] at 15:01 07 December 2014 40 S. R. Myers et al.
cotinine via immunoassay. Amniotic fluid samples were extracted and analyzed for the presence of polycyclic aromatic hydrocarbons (PAHs). A clear correlation was found between levels of maternal smoking and PAHs in the amniotic fluid.Amniotic fluid 1-hydroxypyrene levels ranged from 1.54 ± 0.12 µg/L in nonsmokers to 11.72 ± 0.67 µg/L in women smoking greater than 2 pks/da, indicating approximately a 10X increase over nonsmokers. Similar results were found 3-hydroxybenzo(a)pyrene, 6-hydroxybenzo(a)pyrene, and 3,6-dihydroxybenzo(a)pyrene, metabolites of the carcinogen benzo(a)pyrene as well as with the 9-hydroxy and 9,10-dihydroxy metabolites of anthracene. The 5-hydroxymethyl metabolite of 5-methylchrysene was found to range in concentrations from 1.65 ± 0.11 µg/L in nonsmokers to 12.67 ± 0.79 µg/L in greater than 2 packs per day smokers.These results demonstrate that amniotic fluid can serve as a biological marker of exposure to tobacco related polycyclic aromatic hydrocarbons. Identification of potentially harmful compounds detected at an early stage of pregnancy may prevent subsequent exposures to the fetus and as a result decrease the risk of potential genotoxic as well as teratogenic events.
“…Obviously, a limitation is that only analytes can be detected that remain stable for an extended period of time (DuBey and Caplan, 1996). Newborn Screening Benzoylecgonine and cotinine, which are metabolites of cocaine and nicotine, respectively, have been determined in newborn DBS to assess the prevalence of the use of cocaine and tobacco products among childbearing women (Henderson et al, 1993, Sosnoff et al, 1996, Henderson et al, 1997, Spector et al, 2007). An inherent limitation here is that positive results will only indicate the mother's use of cocaine or tobacco near the time of delivery, thus only offering a limited view on the use during pregnancy.…”
About a century after its first described application by Ivar Bang, the potential of sampling via dried blood spots (DBS) as an alternative for classical venous blood sampling is increasingly recognized. Perhaps best known is the use of DBS in newborn screening programs, ignited by the hallmark paper by Guthrie and Susi half a century ago. However, it is only recently that both academia and industry have recognized the many advantages that DBS sampling may offer for bioanalytical purposes, as reflected by the strong increase in published reports during the last few years. Currently, major DBS applications include newborn screening for metabolic disorders, epidemiological surveys (e.g. HIV monitoring), therapeutic drug monitoring (TDM), as well as toxicology. In this review, we provide a comprehensive overview of the distinct subdisciplines of toxicology for which DBS sampling has been applied. DBS sampling for toxicological evaluation has been performed from birth until autopsy, aiming at the assessment of therapeutic drugs, drugs of abuse, environmental contaminants, toxins, as well as (trace) elements, with applications situated in fields as toxicokinetics, epidemiology and environmental and forensic toxicology. We discuss the strengths and limitations of DBS in the different subdisciplines and provide future prospects for the use of this promising sampling technique in toxicology.
“…Packaging DBS specimens in multiple layers protects mail handlers from accidental exposure and ensures specimen integrity during shipping. Table 1 provides a list of the available drugs of abuse assays with dried blood spot in the literature [19][20][21][22][23][24][25][26][27]. For the sake of clarity, data have been presented by individual drug categories (as opposed to the individual studies).…”
Section: Dbs Specimens Drying Storage and Transportationmentioning
The present article will provide an overview of use of dried blood sampling method for analysis of drug of abuse. Relatively short half life and instability in blood, calls for alternative sampling method for determination of drugs of abuse. Dried blood spot (DBS) method has many advantages over the conventional sampling methods. The available method for DBS sample collection, storage and transport is described here. The techniques involved in and the factors that may influence the accuracy and reproducibility of the DBS methods for determination of drugs of abuse are presented. The DBS sampling has the potential to be a useful technique to detect drugs of abuse. The use of DBS for any drug should be judged against the potential error involved with the method.
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