Honors Theses
Date of Award
2004
Document Type
Undergraduate Thesis
Department
Biology
First Advisor
John Williamson
Relational Format
Dissertation/Thesis
Abstract
There are several classes of anticancer drugs, including the antimicrotubule drugs, which halt mitosis by interfering with the activity of microtubules, the cylindrical protein polymers that play a role in segregating chromosomes during mitosis. While most antimicrotubule drugs act by destabilizing the microtubule polymer and reducing microtubule assembly, paclitaxel, a drug first isolated from the bark of Taxus brevefolia, halts mitosis by stabilizing microtubules, thus interfering with the dynamics of polymerization and depolymerization that are crucial to their function. In light of the mounting resistance to paclitaxel, it is more important than ever to discover new drugs with a similar mechanism of action. Our research group has discovered a novel compound, acetic acid 2,2'-thiobis-, bis [(methylene substituted)hydrazide], that has the same effect on tubulin as paclitaxel. The purpose of this study was to use DNA microarrays to compare the gene expression profile of paclitaxel and our lab's new compound in A549 non-small cell lung cancer cells. DNA microarrays are small glass slides or silicon chips whose ordered arrays of thousands of DNA sequences hybridize with fluorescently labeled messenger RNA probes. A laser excites the fluorescent labels. and the relative gene expression of each gene is measured as the fluorescent intensity of IV each spot. However, microarray work is very complex and requires a considerable amount and variety of equipment and materials. Since our lab did not have the necessary materials or any background knowledge, extensive preparation of the lab was necessary to initiate a project of this magnitude. The study was divided into Part I, the preparatory steps, and Part II, the experimental steps. I was responsible for Part I and thus reviewed literature, learned techniques, adapted cell culture and RNA extraction protocols, purchased materials, set up the laboratory, and designed a basic scheme for the experiment. These steps required extensive research and took two-and-a-half years to complete. As the preparatory work took longer than expected, we are just now nearing the start of the experimental phase of the project. We intend to conduct the study as follows. A549 cells will be cultured and treated with varying concentrations of paclitaxel and acetic acid 2,2'-thiobis-, bis [(methylene substituted)hydrazide], RNA will be extracted, labeled, and hybridized to microarrays, the microarrays will be scanned, and the gene expression profiles induced by each drug will be measured. We hope that our study will help advance the use of microarrays as a tool for drug screening that will accelerate the pace of anticancer drug discovery and development.
Recommended Citation
Ellzey, Jennifer Diane, "The Use of DNA Microarrays to Compare the Gene Expression Profiles of Paclitaxel and Acetic Acid 2,2'-thiobis, bis [[(2-hydroxyphynyl) methylene]hydrazid] in A549 Cells: Part 1" (2004). Honors Theses. 1995.
https://egrove.olemiss.edu/hon_thesis/1995
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