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Dissertation
Development of a 'genetic signature of environmental lead exposure' in wild Peromyscus using combinatorial data from cDNA microarrays and blood metabolites
Doctor of Philosophy (Ph.D.), Drexel University
Jun 2008
DOI:
https://doi.org/10.17918/etd-2796
Abstract
A study of environmental toxicology must be able to identify the biomarkers of one or a few related effectors among a myriad of toxicants affecting diverse biological factors in one or more organisms residing in a contaminated environment and at present, no available technique meets this unique requirement. Lead (Pb) toxicity remains an important environmental toxicological problem on a global scale because of the prevalence of lead exposure to adults and children and its impact on public health (Lanphear, 2007; Hu, et al., 2007). In addition, lead exposure equally affects organisms in natural ecosystems, since lead is ubiquitously found in the environment both as a contaminant from man made materials and natural sources. In addition, the lead is not metabolized in the body, which makes it ideal for the preliminary detection of biomarkers for environmental toxicants. The fundamental goal of my research study was to identify and assess the effectiveness of DNA microarray technology for detection of the biological impact of environmental lead (Pb). I worked it out by identifying correlation between gene expression data from the DNA microarray and conventional toxicological data, such as change of blood Pb and heme concentrations, resulting from environmental lead exposure. I linked the gene expression profiles to the well known lead inducible biochemical processes, to discover 'genetic signature of lead exposure' in the liver and spleen of laboratory Peromyscus maniculatus and Rattus norvagicus, two widely available rodents. I used this laboratory data to develop the genetic signature of environmental lead in the wild Peromyscus maniculatus collected from contaminated field. I found that lead significantly affected expression of the nuclear genes of NADH dehydrogenase and cytochrome oxidase of mitochondrial electron transport system, acyl CoA metabolism, calmodulin, a multifunctional Ca-binding protein, and heat shock protein-1 (90KDa) from stress pathway. However, in these rodents lead induced anemia without affecting the expression of genes in hemoglobin metabolism.
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Details
- Title
- Development of a 'genetic signature of environmental lead exposure' in wild Peromyscus using combinatorial data from cDNA microarrays and blood metabolites
- Creators
- Amitabha Basu - DU
- Contributors
- James Robert Spotila (Advisor) - Drexel University (1970-)
- Awarding Institution
- Drexel University
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- Bioscience and Biotechnology [Historical]; College of Arts and Sciences; Drexel University
- Other Identifier
- 2796; 991014632514504721