Author

Kathryn Gold

Document Type

Honors Capstone Project

Date of Submission

Spring 5-1-2006

Capstone Advisor

Dr. Thomas Fondy

Honors Reader

Dr. John Belote

Capstone Major

Biology

Capstone College

Arts and Science

Audio/Visual Component

no

Capstone Prize Winner

no

Won Capstone Funding

no

Honors Categories

Social Sciences

Subject Categories

Biology

Abstract

Multinucleation occurs in neoplastic cells that have been treated with cytochalasin B, a fungal toxin that disrupts actin microfilament structures. When the actin cytoskeleton is disrupted, contractile ring formation and cytokinesis are inhibited. In normal cells cytochalasin B prevents the cells from entering the cell cycle. However in neoplastic cells, since cytokinesis no longer occurs, the dividing cell becomes enlarged and heavily multinucleated. We propose that enlarged leukemia cells may be more sensitive to ultrasound treatment because of their increased size and weakened cytoskeletal structure. To determine the differential chemical and physical response of enlarged, multinucleated cells in comparison with non-enlarged mononucleated leukemia cells, physical separation of the large and small cells is needed. Using 19 μ steel mesh, a filter system was devised to separate enlarged cells greater than 19 μ in diameter from normal leukemia cells with diameters of 15 μ by settling through a 3.5 cm diameter 19 μ stainless steel mesh sieve with no hydrostatic head and no fluid flow through the filter. The distribution of cells sizes was determined with a Coulter Counter, and the viability was determined by hemocytometer counts, re-growth assays, and cloning assays in agarose. We used the purified cells from this experiment to test the cells’ susceptibility to damage by ultrasound. Acoustic cavitation produced by ultrasound is the process by which high intensity acoustic fields in liquids lead to the creation and oscillation of cavities or gas bubbles. Previous research has shown that ultrasound can transiently disrupt cell membranes and, thereby, facilitate the loading of drugs and genes into viable cells without killing the cells. In our experiments, rather, we sought to determine whether there was a sonic sensitivity in cells treated with cytochalasin B that can lead to cell disruption and cell death, which might be exploitable as a potential modality in leukemia therapy. By exposing both CBtreated and control U937 leukemia cells to ultrasound, we have found that at greater lengths of sonic exposure, the CB-treated cells are more damaged than the control cells. Furthermore, we found that there was a statistically significant retardation in growth rate of sonicated CB-treated cells two and six days post-sonication. This same response to the ultrasound was not seen in the control cells. This physical treatment may be applicable to enhancing the cytotoxic effects of microfilament agents in treatment of leukemia in pre-clinical animal models, and may introduce ultrasound as a physical modality in leukemia treatment

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Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.

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