Academic journal article Environmental Health Perspectives

In Utero Environmental Tobacco Smoke Exposure Alters Gene Expression in Lungs of Adult BALB/c Mice

Academic journal article Environmental Health Perspectives

In Utero Environmental Tobacco Smoke Exposure Alters Gene Expression in Lungs of Adult BALB/c Mice

Article excerpt

The incidence of asthma and allergy has increased dramatically during the past 30 years, primarily in industrialized countries (Eder et al. 2006). Although improved availability and quality of medical care account for some of this increase, the magnitude of the increase surpasses the rate of improvement in health care delivery within these countries. Furthermore, the rate at which this increase has occurred exceeds the generational time of these countries, thereby eliminating a strictly genetic etiology. Consequently, environmental exposures have become the focus of research on the rising incidence of asthma and allergy as well as many other complex diseases. The National Institute of Environmental Health Sciences spearheads programs specifically to define and measure environmental exposures critical in human disease. The new Exposure Biology Program within the Genes and Environment Initiative of the National Institutes of Health targets gene and environmental exposure interactions resulting in human disease.

Development of complex diseases or disorders, including asthma, allergy, atherosclerosis, diabetes, and obesity, has been linked to multiple genes or quantitative trait loci within mammalian genomes (Casas et al. 2006; Shah et al. 2006). Multigene interactions are now suspected in most complex diseases (Chan et al. 2006; Motsinger et al. 2007; Yang et al. 2005). Increasingly, gene--environment inter-actions are also being examined for a role in the etiology of complex diseases (Colilla et al. 2003; Criswell et al. 2006; van Dellen et al. 2005; Williams et al. 2006). Through generalized fetal stress or specific biochemical reactions, in utero environmental exposures appear to mediate complex chronic diseases (cardiovascular disease, obesity, diabetes, asthma) having recognized genetic components (Genuis 2006; Martinez 2007; Okubo and Hogan 2004). Recent findings implicate in utero environmental exposures in developmental disorders such as autism (Ashwood et al. 2006). Although mild-to-moderate environmental exposures may not alter basic genetic information (DNA sequence), these exposures can determine the expression or repression of essential genes at developmentally critical points (Dolinoy et al. 2007; Li et al. 2003), thus contributing to chronic disease.

Altered lung function, increased asthma risk, and persistent lung function deficits in children (Gilliland et al. 2000, 2001; Li et al. 2000) have been associated with maternal smoking during pregnancy (in utero exposure). Environmental tobacco smoke (ETS) aggravates childhood asthmatic responses (Gilliland et al. 2000; Lindfors et al. 1999; Mannino et al. 2001), and premature adult cardiovascular disease in mice (Yang et al. 2004) is promoted by in utero ETS exposure. Altered lung function, exacerbation of symptoms, and acceleration of the disease processes seen with smoke exposure might arise from direct injury suffered by a developing fetus, by alteration of fetal gene expression, or through a combination of fetal injury and protective alteration of gene expression. Fetal sensitivity to ETS may be heightened, or ETS components may bioaccumulate as demonstrated by higher cotinine levels in neonates compared with their nonsmoking mothers who had received ETS exposure during pregnancy (Perera etal. 2004).

Ovalbumin (OVA) is an allergen commonly used in rodent models of allergic asthma. OVA sensitization by ip injection followed by inhalation challenge with OVA aerosol elicits expansion of the T-helper 2 (Th2) lymphocyte population. Production of Th2 cytokines follows, leading to airway hyperresponsiveness (AHR) and inflammation characterized by eosinophilia and appearance of OVA-specific immunoglobulin (Ig) E (Zhang et al. 1997). This sensitization and challenge protocol does not mimic the typical human experience of aerosol-only sensitization and challenge (Bice et al. 2000). However, aerosol-only OVA exposure of mice results in little or no OVA-specific serum IgE, and no eosinophilic inflammatory response. …

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