Growth and development requires the temporal and spatial coordinated expression of genes and gene products. During this critical time, in utero and early postnatal exposure to toxicants has the potential to affect gene expression, altering organ structure and physiological function. However, only limited attention has been paid to the effects of environmentally relevant exposures to toxicants during these critical periods of development. Inorganic arsenic is a ubiquitous environmental toxicant, found in high concentrations throughout the world. Drinking water exposures to high levels of arsenic either in utero or during early childhood development led to an increased risk of dying from lung cancers and chronic lung disease in adults. Our own work in animal models has demonstrated that following in utero and early postnatal exposure to arsenic, airway response to methacholine was increased in a dose dependent manner. This change appears to be permanent and the response is specific for the early developmental exposure. While exposures from ingestion of arsenic can lead to alterations, the inhalation route of exposure is also relevant to the lung. In utero and/or postnatal exposure to cigarette smoke, ambient urban air particles or metals leads to increased airway reactivity, decreased surface to volume ratios in the lung and altered lung function in the offspring. Therefore, we hypothesize that inhalation of dusts containing arsenic during sensitive developmental times will result in altered pulmonary function and structure in adults. The evaluation of the direct effects of inhaled arsenic and the potential interactions of inhaled arsenic and ingested arsenic will be the emphasis of this project. We will evaluate four aims. The first three Aims will define sensitive exposure times necessary to produce alterations in lung structure and function in the offspring:
Aim 1 will examine the effects of inhalation of arsenic and arsenic containing particles to pregnant mice (in utero exposure);
Aim 2 will examine the effects of early postnatal exposures to these compounds and Aim 3 will examine the effect of combined in utero and postnatal exposures.
Aim 4 will evaluate the effect of inhalation in combination with ingestion of arsenic.
|Gonzales, Patricia; Felix, Omar; Alexander, Caitlin et al. (2014) Laboratory dust generation and size-dependent characterization of metal and metalloid-contaminated mine tailings deposits. J Hazard Mater 280:619-26|
|Severson, Paul L; Vrba, Lukas; Stampfer, Martha R et al. (2014) Exome-wide mutation profile in benzo[a]pyrene-derived post-stasis and immortal human mammary epithelial cells. Mutat Res Genet Toxicol Environ Mutagen 775-776:48-54|
|Boitano, Scott; Hoffman, Justin; Tillu, Dipti V et al. (2014) Development and evaluation of small peptidomimetic ligands to protease-activated receptor-2 (PAR2) through the use of lipid tethering. PLoS One 9:e99140|
|Sollome, James J; Thavathiru, Elangovan; Camenisch, Todd D et al. (2014) HER2/HER3 regulates extracellular acidification and cell migration through MTK1 (MEKK4). Cell Signal 26:70-82|
|Medeiros, Matthew; Le, Tam Minh; Troup, Daniel et al. (2014) Expression Of Selected Pathway-Marker Genes In Human Urothelial Cells Exposed Chronically To A Non-Cytotoxic Concentration Of Monomethylarsonous Acid. Toxicol Rep 1:421-434|
|Crosbie, Ewan; Sorooshian, Armin; Monfared, Negar Abolhassani et al. (2014) A Multi-Year Aerosol Characterization for the Greater Tehran Area Using Satellite, Surface, and Modeling Data. Atmosphere (Basel) 5:178-197|
|Miao, Ziheng; Carreón-Diazconti, Concepcion; Carroll, Kenneth C et al. (2014) The impact of biostimulation on the fate of sulfate and associated sulfur dynamics in groundwater. J Contam Hydrol 164:240-50|
|Ramirez-Andreotta, Monica D; Brusseau, Mark L; Artiola, Janick F et al. (2014) Environmental Research Translation: enhancing interactions with communities at contaminated sites. Sci Total Environ 497-498:651-64|
|Csavina, Janae; Field, Jason; Félix, Omar et al. (2014) Effect of wind speed and relative humidity on atmospheric dust concentrations in semi-arid climates. Sci Total Environ 487:82-90|
|Beamer, P I; Sugeng, A J; Kelly, M D et al. (2014) Use of dust fall filters as passive samplers for metal concentrations in air for communities near contaminated mine tailings. Environ Sci Process Impacts 16:1275-81|
Showing the most recent 10 out of 312 publications