Diesel exhaust particles cause increased levels of DNA deletions after transplacental exposure in mice

Reliene, Ramune; Hlavacova, Alexandra; Mahadevan, B; Baird, William M.; Schiestl, Robert H.

doi:10.1016/j.mrfmmm.2004.11.010

Cited by 44 publications

(28 citation statements)

References 38 publications

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“…Evidence for transplacental cytokine transport is decidedly mixed with a paucity of direct labeling studies. Maternally ingested diesel particles are associated with oxidative DNA damage in embryos (27), but, to our knowledge, no detection of particles in embryos/fetuses has been reported. Elegant, albeit indirect, studies using transgenic mice lacking cytokine receptors for IL-4 or IL-13, pregnant with wild-type (heterozygous) offspring, showed that maternal injection with receptor ligands had no effect on cytokine receptor signaling in fetal tissues, strongly suggesting that IL-4 and IL-13 do not cross the placenta (28).…”

Section: Discussionmentioning

confidence: 74%

Maternal Diesel Inhalation Increases Airway Hyperreactivity in Ozone-Exposed Offspring

Auten¹,

Gilmour

Krantz

et al. 2012

Am J Respir Cell Mol Biol

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Air pollutant exposure is linked with childhood asthma incidence and exacerbations, and maternal exposure to airborne pollutants during pregnancy increases airway hyperreactivity (AHR) in offspring. To determine if exposure to diesel exhaust (DE) during pregnancy worsened postnatal ozone-induced AHR, timed pregnant C57BL/6 mice were exposed to DE (0.5 or 2.0 mg/m 3 ) 4 hours daily from Gestation Day 9-17, or received twice-weekly oropharyngeal aspirations of the collected DE particles (DEPs). Placentas and fetal lungs were harvested on Gestation Day 18 for cytokine analysis. In other litters, pups born to dams exposed to air or DE, or to dams treated with aspirated diesel particles, were exposed to filtered air or 1 ppm ozone beginning the day after birth, for 3 hours per day, 3 days per week for 4 weeks. Additional pups were monitored after a 4-week recovery period. Diesel inhalation or aspiration during pregnancy increased levels of placental and fetal lung cytokines. There were no significant effects on airway leukocytes, but prenatal diesel augmented ozone-induced elevations of bronchoalveolar lavage cytokines at 4 weeks. Mice born to the high-concentration dieselexposed dams had worse ozone-induced AHR, which persisted in the 4-week recovery animals. Prenatal diesel exposure combined with postnatal ozone exposure also worsened secondary alveolar crest development. We conclude that maternal inhalation of DE in pregnancy provokes a fetal inflammatory response that, combined with postnatal ozone exposure, impairs alveolar development, and causes a more severe and long-lasting AHR to ozone exposure.Keywords: diesel; fetal inflammation; ozone; airway hyperreactivity Increasing asthma prevalence among children in industrialized nations has stimulated a number of investigations focused on early life exposures to air pollutants (1). Maternal exposures to a variety of inhaled atmospheric pollutants, including side and mainstream tobacco smoke, diesel exhaust (DE), and ozone, have been linked in epidemiologic studies to asthma and other respiratory diseases in children (2-4). Animal models aimed at deciphering the mechanisms by which maternal exposures during pregnancy are linked to childhood asthma have largely focused on pathways relevant to allergic asthma (5).In addition to allergic sensitization, in utero exposure to air pollutants may also affect nonspecific pulmonary responses, such as airway hyperreactivity (AHR) (6). It has already been shown that fetal pulmonary inflammatory challenges are linked with impaired postnatal alveolar development (7-9), which affects airway stability and AHR (10). Previous studies have shown that maternal exposure to DE during pregnancy modified mouse placental cytokines relevant to airway inflammation (11), and lowered the threshold for AHR in ovalbuminsensitized offspring (12).We have previously shown that a standardized urban particulate delivered by oropharyngeal aspiration during pregnancy induced placental inflammatory cytokine expression and worsened neonatal ozone-induced...

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Section: Discussionmentioning

confidence: 74%

Maternal Diesel Inhalation Increases Airway Hyperreactivity in Ozone-Exposed Offspring

Auten¹,

Gilmour

Krantz

et al. 2012

Am J Respir Cell Mol Biol

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“…Evidence from epidemiological studies indicates a strong association between ambient concentrations of air pollutants, including PM, and poor developmental outcomes, such as low birth weight (3,19,23) preterm birth (34,37), and intrauterine growth restriction (10,36). Animal studies have confirmed these outcomes (25,38,40,44) and shown genetic and epigenetic changes in animals maternally exposed to air pollution (32). Consequences can be seen manifested as poor neurological outcomes (39,49), increased airway inflammation, and respiratory dysfunction (18).…”

mentioning

confidence: 99%

Early life exposure to air pollution induces adult cardiac dysfunction

Gorr

Velten²,

Nelin

et al. 2014

American Journal of Physiology-Heart and Circulatory Physiology

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Exposure to ambient air pollution contributes to the progression of cardiovascular disease, particularly in susceptible populations. The objective of the present study was to determine whether early life exposure to air pollution causes persistent cardiovascular consequences measured at adulthood. Pregnant FVB mice were exposed to filtered (FA) or concentrated ambient particulate matter (PM2.5) during gestation and nursing. Mice were exposed to PM2.5 at an average concentration of 51.69 μg/m3 from the Columbus, OH region for 6 h/day, 7 days/wk in utero until weaning at 3 wk of age. Birth weight was reduced in PM2.5 pups compared with FA (1.36 ± 0.12 g FA, n = 42 mice; 1.30 ± 0.15 g PM2.5, n = 67 P = 0.012). At adulthood, mice exposed to perinatal PM2.5 had reduced left ventricular fractional shortening compared with FA-exposed mice (43.6 ± 2.1% FA, 33.2 ± 1.6% PM2.5, P = 0.001) with greater left ventricular end systolic diameter. Pressure-volume loops showed reduced ejection fraction (79.1 ± 3.5% FA, 35.5 ± 9.5% PM2.5, P = 0.005), increased end-systolic volume (10.4 ± 2.5 μl FA, 39.5 ± 3.8 μl PM2.5, P = 0.001), and reduced dP/d t maximum (11,605 ± 200 μl/s FA, 9,569 ± 800 μl/s PM2.5, P = 0.05) and minimum (−9,203 ± 235 μl/s FA, −7,045 ± 189 μl/s PM2.5, P = 0.0005) in PM2.5-exposed mice. Isolated cardiomyocytes from the hearts of PM2.5-exposed mice had reduced peak shortening (%PS, 8.53 ± 2.82% FA, 6.82 ± 2.04% PM2.5, P = 0.003), slower calcium reuptake (τ, 0.22 ± 0.09 s FA, 0.26 ± 0.07 s PM2.5, P = 0.048), and reduced response to β-adrenergic stimulation compared with cardiomyocytes isolated from mice that were exposed to FA. Histological analyses revealed greater picro-sirius red-positive-stained areas in the PM2.5 vs. FA group, indicative of increased collagen deposition. We concluded that these data demonstrate the detrimental role of early life exposure to ambient particulate air pollution in programming of adult cardiovascular diseases and the potential for PM2.5 to induce persistent cardiac dysfunction at adulthood.

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“…Studies in preclinical models have shown that transplacental or lactational exposures can result in cancers and/or adverse reproductive effects in offspring, not just in the young, but also in adults. Transplacental carcinogens studied in preclinical models include PAHs (Anderson et al, 1985; Loktionov et al, 1992; Miller, 1994; Miller et al, 2000; Reliene et al, 2005), nitrosamines (Anderson et al, 1989; Hecht, 1998), arsenic (Shen et al, 2007; Waalkes et al, 2004) and cooked food mutagens (Hasegawa et al, 1995; Josyula et al, 2000). Yu et al (2006a) showed that in utero exposure to DBP can result in a high incidence of mortality in young adults due to aggressive T-cell lymphoblastic lymphoma, a disease that is also observed in human adolescents (Lightfoot and Roman, 2004).…”

Section: Introductionmentioning

confidence: 99%

DNA methylation in lung tissues of mouse offspring exposed in utero to polycyclic aromatic hydrocarbons

Fish

Benninghoff

2017

Food and Chemical Toxicology

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Polycyclic aromatic hydrocarbons (PAHs) comprise an important class of environmental pollutants that are known to cause lung cancer in animals and are suspected lung carcinogens in humans. Moreover, evidence from cell-based studies points to PAHs as modulators of the epigenome. The objective of this work was to assess patterns of genome-wide DNA methylation in lung tissues of adult offspring initiated in utero with the transplacental PAH carcinogens dibenzo[def,p]chrysene (DBC) or benzo[a]pyrene (BaP). Genome-wide methylation patterns for normal (not exposed), normal adjacent and lung tumor tissues obtained from adult offspring were determined using methylated DNA immunoprecipitation (MeDIP) with the NimbleGen mouse DNA methylation CpG island array. Lung tumor incidence in 45-week old mice initiated with BaP was 32%, much lower than that of the DBC-exposed offspring at 96%. Also, male offspring appeared more susceptible to BaP as compared to females. Distinct patterns of DNA methylation were associated with non-exposed, normal adjacent and adenocarcinoma lung tissues, as determined by principal components, hierarchical clustering and gene ontology analyses. From these methylation profiles, a set of genes of interest was identified that includes potential important targets for epigenetic modification during the process of lung tumorigenesis in animals exposed to environmental PAHs.

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Diesel exhaust particles cause increased levels of DNA deletions after transplacental exposure in mice

Cited by 44 publications

References 38 publications

Maternal Diesel Inhalation Increases Airway Hyperreactivity in Ozone-Exposed Offspring

Maternal Diesel Inhalation Increases Airway Hyperreactivity in Ozone-Exposed Offspring

Early life exposure to air pollution induces adult cardiac dysfunction

DNA methylation in lung tissues of mouse offspring exposed in utero to polycyclic aromatic hydrocarbons

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