An In Vitro Versus In Vivo Toxicogenomics Investigation of Pre-natal Exposures to Tobacco Smoke
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ABSTRACT:
ORGANISM(S): Mus musculus Homo sapiens
PROVIDER: GSE96978 | GEO | 2017/04/03
SECONDARY ACCESSION(S): PRJNA380260
REPOSITORIES: GEO
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Project description:Lab-grown human bronchial epithelium model (Epiairway) was exposed to cigarette smoke or filtered air. RNA was harvested from the Epiairway tissue and underwent transcriptomic analysis.
2017-04-03 | GSE96976 | GEO
Project description:Pregnant mice (Dams) were exposed to cigarette smoke or filtered air. Lung tissue and RNA were harvested from the lungs of the Dams and their offspring and underwent transcriptomic analysis.
2017-04-03 | GSE96977 | GEO
Project description:An In Vitro Versus In Vivo Toxicogenomics Investigation of Pre-natal Exposures to Tobacco Smoke
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Project description:Approximately 1 million women smoke during pregnancy despite evidence demonstrating serious juvenile and/or adult diseases being linked to early-life exposure to cigarette smoke. Susceptibility could be determined by factors in previous generations, that is, prenatal or "maternal" exposures to toxins. Prenatal exposure to airborne pollutants such as mainstream cigarette smoke has been shown to induce early-life insults (i.e., gene changes) in Offspring that serve as biomarkers for disease later in life. In this investigation, we have evaluated genome-wide changes in the lungs of mouse Dams and their juvenile Offspring exposed prenatally to mainstream cigarette smoke. An additional lung model was tested alongside the murine model, as a means to find an alternative in vitro, human tissue-based replacement for the use of animals in medical research. Our toxicogenomic and bio-informatic results indicated that in utero exposure altered the genetic patterns of the fetus, which could put them at greater risk for developing a range of chronic illnesses in later life. The genes altered in the in vitro, cell culture model were reflected in the murine model of prenatal exposure to mainstream cigarette smoke. The use of alternative in vitro models derived from human medical waste tissues could be viable options to achieve human endpoint data and conduct research that meets the remits for scientists to undertake the 3Rs practices.
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Project description:The battery of regulatory tests used to evaluate the risk of novel tobacco products such as heated tobacco products (THPs) presents some limitations including a bias towards the apical endpoint tested, and limited information on the mode of action. This is driving a paradigm shift to more holistic systems biology approaches. In this study, we used RNA-sequencing to compare the transcriptomic perturbations following acute exposure of a 3D airway tissue to the aerosols from two commercial THPs and a reference 3R4F cigarette. 2809 RNAs were differentially expressed for the 3R4F treatment and 115 and 2 RNAs for the two THPs (pFDR < 0.05, FC > 1.5), respectively. The relationship between the identified RNA features and gene ontologies were mapped showing a strong association with stress response, xenobiotics metabolism, and COPD-related terms for 3R4F. In contrast, fewer ontologies were found enriched for the THPs aerosols. "Response to wounding" was a common COPD-related term over-represented for the two THPs but at a reduced significance. Quantification of a cytokine panel post-exposure confirmed a pro-inflammatory effect of cigarette smoke but not for THPs. In conclusion, THPs have a reduced impact on gene expression compared to 3R4F.
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Project description:IntroductionTobacco smoke pollution (TSP) has been identified as a serious public health threat. Although the number of jurisdictions that prohibit smoking in public places has increased rapidly, just a few successful attempts have been made to pass similar laws prohibiting smoking in cars, where the cabin space may contribute to concentrated exposure. In particular, TSP constitutes a potentially serious health hazard to children because of prolonged exposure and their small size.MethodsThe present study investigated the levels of TSP in 18 cars via the measurement of fine respirable particles (<2.5 microns in diameter or PM(2.5)) under a variety of in vivo conditions. Car owners smoked a single cigarette in their cars in each of five controlled air-sampling conditions. Each condition varied on movement of the car, presence of air conditioning, open windows, and combinations of these airflow influences.ResultsSmoking just a single cigarette in a car generated extremely high average levels of PM(2.5): more than 3,800 microg/m3 in the condition with the least airflow (motionless car, windows closed). In moderate ventilation conditions (air conditioning or having the smoking driver hold the cigarette next to a half-open window), the average levels of PM(2.5) were reduced but still at significantly high levels (air conditioning = 844 microg/m3; holding cigarette next to a half-open window = 223 microg/m3).DiscussionThis study demonstrates that TSP in cars reaches unhealthy levels, even under realistic ventilation conditions, lending support to efforts occurring across a growing number of jurisdictions to educate people and prohibit smoking in cars in the presence of children.
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Project description:The interleukin-1 receptor antagonist (IL1RN) is a potent anti-inflammatory cytokine. In the present study, association of the human IL1RN gene polymorphisms with asthma, bronchial hyperresponsiveness and forced expiratory volume in one second/forced vital capacity ratio was tested and the data was stratified by environmental tobacco smoke exposure in order to investigate a gene-smoking interaction. In an unselected subset (n = 921) of the Isle of Wight birth (UK) cohort, which has previously been evaluated for asthma and related manifestations at ages 1, 2, 4 and 10 yrs, three IL1RN single nucleotide polymorphisms (SNP) were genotyped. Logistic regression and repeated measurement models for tests of association using a representative SNP rs2234678 were used, as all SNPs tested were in strong linkage disequilibrium. In the overall analysis, the SNP rs2234678 was not associated with asthma. However, in the stratum with maternal smoking during pregnancy the rs2234678 GG genotype significantly increased the relative risk of asthma in children, both in analyses of repeated asthma occurrences and persistent asthma. In conclusion, the present results show that in the first decade of life, the gene-environment interaction of the interleukin-1 receptor antagonist gene polymorphism rs2234678 and maternal smoking during pregnancy increased the risk for childhood asthma.
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Project description:Although parents of triplets experience substantial mental distress, research about this increasing population has primarily focused on physical health risks of triplets and mothers, failing to capture the subjective wellbeing of parents. Accordingly, this study aimed to understand first-hand experience of parents of triplets, using thematic analysis of semi-structured interviews participated by eight parents (four couples: Age M = 48.63, SD = 10.61 years). Six themes were identified: (1) Negative and (2) Positive experiences of raising triplets prenatally and postnatally, (3) Social, psychological, and material support, (4) Experiences and challenges specific to mothers and (5) fathers, and (6) Advice for future parents. These themes suggest that being reassured and accepting support from others are particularly essential in reducing stress and anxiety. Self-compassion interventions were recommended to support the wellbeing of parents of triplets. Our findings will help parents of triplets, their social circles, and healthcare workers to develop effective approaches to reduce the mental health difficulties that this under-researched population experiences.
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Project description:Childhood environmental tobacco smoke (ETS) exposure is a risk factor for adverse health outcomes and may disproportionately burden lower socioeconomic status groups, exacerbating health disparities. We explored associations of demographic factors, stressful life events, and chemical co-exposures, with cotinine levels, among girls in the CYGNET Study. Data were collected from families of girls aged 6-8 years old in Northern California, through clinic exams, questionnaires and biospecimens (n = 421). Linear regression and factor analysis were conducted to explore predictors of urinary cotinine and co-exposure body burdens, respectively. In unadjusted models, geometric mean cotinine concentrations were higher among Black (0.59 ug/g creatinine) than non-Hispanic white (0.27), Asian (0.32), or Hispanic (0.34) participants. Following adjustment, living in a rented home, lower primary caregiver education, and lack of two biologic parents in the home were associated with higher cotinine concentrations. Girls who experienced parental separation or unemployment in the family had higher unadjusted cotinine concentrations. Higher cotinine was also associated with higher polybrominated diphenyl ether and metals concentrations. Our findings have environmental justice implications as Black and socio-economically disadvantaged young girls experienced higher ETS exposure, also associated with higher exposure to other chemicals. Efforts to reduce ETS and co-exposures should account for other disparity-related factors.
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Project description:In vitro Omics analysis (i.e. transcriptome) is suggested to predict in vivo toxicity and adverse effects in humans, although the causal link between high-throughput data and effects in vivo is not easily established. Indeed, the chemical-organism interaction can involve processes, such as adaptation, not established in cell cultures. Starting from this consideration we investigate the transcriptomic response of immortalized thyrocytes to ethylenthiourea and chlorpyrifos. In vitro data revealed specific and common genes/mechanisms of toxicity, controlling the proliferation/survival of the thyrocytes and unrelated hematopoietic cell lineages. These results were phenotypically confirmed in vivo by the reduction of circulating T4 hormone and the development of pancytopenia after long exposure. Our data imply that in vitro toxicogenomics is a powerful tool in predicting adverse effects in vivo, experimentally confirming the vision described as Tox21c (Toxicity Testing in the 21st century) although not fully recapitulating the biocomplexity of a living animal.
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