Prenatal Tobacco Smoke and Expression in Airways

  • Van Winkle, Laura S, (PI)

Project: Research project

Project Details

Description

DESCRIPTION (provided by applicant): Metabolism is a key step in eliminating xenobiotics from the body. Despite the fundamental importance of metabolism in determining the potency of contaminants and carcinogens, little is known about the influence of exposures early in life on the adult expression of these systems, particularly in females. Environmental tobacco smoke (ETS) is one of the most ubiquitous sources of pulmonary exposure to known human carcinogens. Widespread exposure of children to ETS is supported by the fact that as many as 85% of children have detectable levels of cotinine in their blood. Yet the effect of early life exposure on adult onset lung diseases such as cancer has received limited attention. We propose to investigate the effect of pre and post-natal ETS exposures on the expression of genes for metabolism and detoxification enzymes in the target organ for airborne carcinogens, the lung. ETS toxicity is of interest in the female population because women develop lung cancer earlier and after less cigarette exposure than men. We propose to investigate female specific alterations in gene expression in the airways. We will examine the effects of ETS exposures on the lung by comparing the gene expression profiles and histopathology of samples obtained from female mice exposed to well characterized aged and diluted side stream tobacco smoke with those from filtered air control mice. The proposed studies will use microarray approaches to define, at the cellular level, the occurrence and persistence of altered gene expression in mice exposed either prenatally or both pre and postnatally to side stream cigarette smoke. We will use an experimental approach that identifies changes in genes as well as pathobiology specific to conducting airways, the site of many changes associated with both smoke exposure and adult onset diseases such as asthma, chronic bronchitis and lung cancer. The central hypothesis is that adult onset lung diseases in females, such as lung cancer and asthma, are related to the ability of the lung to metabolically activate compounds and this is profoundly influenced by the history of prior exposure to such compounds, particularly in utero. We will address the central hypothesis through 3 Specific Aims that will define: 1) the effect of pre and postnatal ETS exposure on gene expression in adult airways, 2) the effect of prenatal ETS exposure on gene expression in infant airways and 3) which changes in infant gene expression persist into adulthood. These studies will thus address the fetal basis of adult diseases of the lung caused by exposure in utero to environmental tobacco smoke.
StatusFinished
Effective start/end date5/1/043/31/08

Funding

  • National Institutes of Health: $147,940.00
  • National Institutes of Health: $148,500.00
  • National Institutes of Health: $150,750.00

ASJC

  • Environmental Science(all)
  • Medicine(all)

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