Genistein (GEN), a soy isoflavone, has been suggested to mediate its biological function mainly as an endocrine disruptor instead of a tyrosine kinase inhibitor in vivo. Despite the hypothesized beneficial effects of GEN, there are concerns about the long-term effects of this compound on human health, especially that of infants and young children. The recent epidemiological findings indicate that there is an increase in the use of asthma or allergy drugs in young adults who have been fed soy formula during infancy as compared to those who have been fed cow milk formula. One important mechanism for development of asthma is that allergens repeatedly stimulate T helper (Th) 2-polarized T-cell immunity in local airway tissue. Our studies have provided evidence that the developing immune system, especially the function of T cells, was altered following oral exposure to GEN at physiologically relevant concentrations in experimental animals. It is hypothesized that developmental exposure to GEN modulates the chromatin structure of Th2 cytokine genes (e.g., IL-4 and IL-13) and, thus, leads to an increase in the hypersensitivity responses to respiratory allergen trimellitic anhydride (TMA) in adult life. To test this hypothesis, two specific aims will be pursued: (1) To determine if developmental exposure to GEN leads to an enhancement in hypersensitivity responses to respiratory allergen TMA in adult life; (2) To determine if developmental exposure to GEN leads to DNA demethylation and chromosome remodeling of Th2 cytokine genes such as IL-4 and IL-13. Results of this investigation will provide a rational basis for understanding the health implications associated with the consumption of this compound. By identifying possible cytokines that are important at increasing risks, by looking at vulnerable periods in life, and by identifying environmental factors which through different mechanisms may be driving the immunological processes (amongst others) that lead to asthma, we will gain a better insight with which to make informed decisions regarding intervention studies.

National Institute of Health (NIH)
National Institute of Environmental Health Sciences (NIEHS)
Exploratory/Developmental Grants (R21)
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Special Emphasis Panel (ZRG1-REB (50))
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Mastin, Patrick
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Virginia Commonwealth University
Schools of Medicine
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