Most cited article - PubMed ID 9150753
DNA adducts in human placenta as related to air pollution and to GSTM1 genotype
Thirty years ago, Northern Bohemia in the Czech Republic was one of the most air polluted areas in Europe. After political changes, the Czech government put forward a research program to determine if air pollution is really affecting human health. This program, later called the "Teplice Program", was initiated in collaboration with scientists from the United States Environmental Protection Agency (US EPA). This cooperation made possible the use of methods on the contemporary level. The very high concentrations of sulphur dioxide (SO2), particulate matter of 10 micrometers or less (PM10), and polycyclic aromatic hydrocarbons (PAHs) present in the air showed, for the first time, the impact of air pollutants on the health of the population in mining districts: adverse pregnancy outcomes, the impact of air pollution on sperm morphology, learning disabilities in children, and respiratory morbidity in preschool children. A surprising result came from the distribution of the sources of pollution: 70% of PM10 pollution came from local heating and not from power plants as expected. Thanks to this result, the Czech government supported changes in local heating from brown coal to natural gas. This change substantially decreased SO2 and PM10 pollution and affected mortality, especially cardiovascular mortality.
- Keywords
- DNA adducts, PAHs, PM2.5, SO2, air pollution, mortality, neurobehavioral changes, pregnancy outcome, sperm abnormalities,
- MeSH
- Air Pollutants * analysis MeSH
- Humans MeSH
- Particulate Matter analysis MeSH
- Child, Preschool MeSH
- Pregnancy MeSH
- Health MeSH
- Air Pollution * analysis MeSH
- Check Tag
- Humans MeSH
- Child, Preschool MeSH
- Pregnancy MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
- Geographicals
- Czech Republic MeSH
- Europe MeSH
- Names of Substances
- Air Pollutants * MeSH
- Particulate Matter MeSH
Three classes of DNA damage were assessed in human placentas collected (2000-2004) from 51 women living in the Teplice region of the Czech Republic, a mining area considered to have some of the worst environmental pollution in Europe in the 1980s. Polycyclic aromatic hydrocarbon (PAH)-DNA adducts were localized and semiquantified using immunohistochemistry (IHC) and the Automated Cellular Imaging System (ACIS). More generalized DNA damage was measured both by (32)P-postlabeling and by abasic (AB) site analysis. Placenta stained with antiserum elicited against DNA modified with 7β,8α-dihydroxy-9α,10α-epoxy-7,8,9,10-tetrahydro-benzo[a]pyrene (BPDE) revealed PAH-DNA adduct localization in nuclei of the cytotrophoblast (CT) cells and syncytiotrophoblast (ST) knots lining the chorionic villi. The highest levels of DNA damage, 49-312 PAH-DNA adducts/10(8) nucleotides, were found by IHC/ACIS in 14 immediately fixed placenta samples. An additional 37 placenta samples were stored frozen before fixation and embedding, and because PAH-DNA adducts were largely undetectable in these samples, freezing was implicated in the loss of IHC signal. The same placentas (n = 37) contained 1.7-8.6 stable/bulky DNA adducts/10(8) nucleotides and 0.6-47.2 AB sites/10(5) nucleotides. For all methods, there was no correlation among types of DNA damage and no difference in extent of DNA damage between smokers and nonsmokers. Therefore, the data show that DNA from placentas obtained in Teplice contained multiple types of DNA damage, which likely arose from various environmental exposures. In addition, PAH-DNA adducts were present at high concentrations in the CT cells and ST knots of the chorionic villi.
- MeSH
- DNA Adducts toxicity MeSH
- Immune Sera MeSH
- Immunohistochemistry MeSH
- Keratinocytes drug effects metabolism MeSH
- Smoking adverse effects MeSH
- Humans MeSH
- Polycyclic Aromatic Hydrocarbons toxicity MeSH
- DNA Damage * drug effects MeSH
- In Vitro Techniques MeSH
- Pregnancy MeSH
- Check Tag
- Humans MeSH
- Pregnancy MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Research Support, N.I.H., Intramural MeSH
- Research Support, U.S. Gov't, Non-P.H.S. MeSH
- Geographicals
- Czech Republic MeSH
- Names of Substances
- DNA Adducts MeSH
- Immune Sera MeSH
- polycyclic aromatic hydrocarbons-DNA adduct MeSH Browser
- Polycyclic Aromatic Hydrocarbons MeSH
Over the last decade or so, a large number of studies have investigated the possible adverse effects of ambient air pollution on birth outcomes. We reviewed these studies, which were identified by a systematic search of the main scientific databases. Virtually all reviewed studies were population based, with information on exposure to air pollution derived from routine monitoring sources. Overall, there is evidence implicating air pollution in adverse effects on different birth outcomes, but the strength of the evidence differs between outcomes. The evidence is sufficient to infer a causal relationship between particulate air pollution and respiratory deaths in the postneonatal period. For air pollution and birth weight the evidence suggests causality, but further studies are needed to confirm an effect and its size and to clarify the most vulnerable period of pregnancy and the role of different pollutants. For preterm births and intrauterine growth retardation (IUGR) the evidence as yet is insufficient to infer causality, but the available evidence justifies further studies. Molecular epidemiologic studies suggest possible biologic mechanisms for the effect on birth weight, premature birth, and IUGR and support the view that the relation between pollution and these birth outcomes is genuine. For birth defects, the evidence base so far is insufficient to draw conclusions. In terms of exposure to specific pollutants, particulates seem the most important for infant deaths, and the effect on IUGR seems linked to polycyclic aromatic hydrocarbons, but the existing evidence does not allow precise identification of the different pollutants or the timing of exposure that can result in adverse pregnancy outcomes.
- MeSH
- Infant MeSH
- Infant Mortality * MeSH
- Humans MeSH
- Infant, Low Birth Weight * MeSH
- Infant, Newborn MeSH
- Pregnancy MeSH
- Pregnancy Outcome MeSH
- Air Pollution adverse effects MeSH
- Check Tag
- Infant MeSH
- Humans MeSH
- Infant, Newborn MeSH
- Pregnancy MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
Genotypes responsible for interindividual differences in ability to activate or detoxify genotoxic agents are recognized as biomarkers of susceptibility. Among the most studied genotypes are human glutathione transferases. The relationship of genetic susceptibility to biomarkers of exposure and effects was studied especially in relation to the genetic polymorphism of glutathione S-transferase M1 (GSTM1). For this review papers reporting the effect of GSTM1 genotype on DNA adducts, protein adducts, urine mutagenicity, Comet assay parameters, chromosomal aberrations, sister chromatid exchanges (SCE), micronuclei, and hypoxanthine-guanine phosphoribosyl transferase mutations were assessed. Subjects in groups occupationally exposed to polycyclic aromatic hydrocarbons, benzidine, pesticides, and 1,3-butadiene were included. As environmentally exposed populations, autopsy donors, coal tar-treated patients, smokers, nonsmokers, mothers, postal workers, and firefighters were followed. From all biomarkers the effect of GSTM1 and N-acetyl transferase 2 was seen in coke oven workers on mutagenicity of urine and of glutathione S-transferase T1 on the chromosomal aberrations in subjects from 1,3-butadiene monomer production units. Effects of genotypes on DNA adducts were found from lung tissue of autopsy donors and from placentas of mothers living in an air-polluted region. The GSTM1 genotype affected mutagenicity of urine in smokers and subjects from polluted regions, protein adducts in smokers, SCE in smokers and nonsmokers, and Comet assay parameters in postal workers. A review of all studies on GSTM1 polymorphisms suggests that research probably has not reached the stage where results can be interpreted to formulate preventive measures. The relationship between genotypes and biomarkers of exposure and effects may provide an important guide to the risk assessment of human exposure to mutagens and carcinogens.
- MeSH
- Biomarkers MeSH
- Genotype MeSH
- Glutathione Transferase genetics MeSH
- Isoenzymes genetics MeSH
- Carcinogens, Environmental toxicity MeSH
- Humans MeSH
- Mutagens toxicity MeSH
- Polymorphism, Genetic * MeSH
- Occupational Exposure MeSH
- Environmental Exposure * MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
- Names of Substances
- Biomarkers MeSH
- Glutathione Transferase MeSH
- Isoenzymes MeSH
- Carcinogens, Environmental MeSH
- Mutagens MeSH