Genetic Susceptibility to Inhaled Particles and GasesEPA Grant Number: U915783
Title: Genetic Susceptibility to Inhaled Particles and Gases
Investigators: Wesselkamper, Scott C.
Institution: New York University
EPA Project Officer: Carleton, James N
Project Period: September 1, 2000 through September 1, 2002
Project Amount: $102,000
RFA: STAR Graduate Fellowships (2000) RFA Text | Recipients Lists
Research Category: Fellowship - Life Sciences , Academic Fellowships , Biology/Life Sciences
The objective of this research project is to determine host genetic determinants that control the development of pulmonary tolerance to repeated inhaled toxicant exposure.
Several approaches are being used to identify genes involved in the development of tolerance. First, it has been demonstrated that inbred strains of mice differ significantly in their ability to develop pulmonary tolerance to inhaled zinc oxide (ZnO, 1 mg/m3). Specifically, the BALB/cByJ (tolerant) and DBA/2J (non-tolerant) inbred mouse strains were determined to be the most contrasting with respect to lung inflammation and injury following single and five successive exposures to ZnO. Quantitative trait linkage analyses with intercross offspring from these two strains are being used to identify chromosomal regions that contain candidate genes involved in tolerance. This quantitative trait linkage data will then be used in conjunction with oligonucleotide microarray experiments to characterize the expression of and identify potential candidate genes present in the chromosomal regions of interest.
An understanding of the genetic basis for inter-individual variation in response to repeated exposure to inhaled toxicants will clarify the molecular mechanism(s) of host response and provide a potential means to identify genetically susceptible individuals, who may be at risk to adverse health effects from inhalation exposures.