The Effects of Dosage and Exposure Time on the Genomic Incorporation of 3'- Azido-2', 3'-Dideoxythymidine (AZT) in TK6 Cells, and the Role of AZT in DNA Methylation
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Authors
Pietras, Sara
Issue Date
1999
Type
Thesis
Language
en_US
Keywords
Alternative Title
Abstract
In 1987 the first anti-AIDs drug, 3'-azido-2', 3'-dideoxythymidine (AZT), was approved.
Today AZT treatment includes persons with human immunodeficiency virus type 1
(HIV -1), of all ages and at all stages of the disease. One AZT treatment group is
pregnant women, as AZT has been shown to significantly reduce the chance of vertical
HIV -1 transmission. However AZT has recently been shown to produce tumors in the
offspring of mice who are treated with it during the last third of pregnancy. In these
studies, we assessed the incorporation of AZT into the genome of human lymphoblastoid
(TK6) cells exposed to the drug for increasing amounts of time, and also in dose
increments. Furthermore, we examined the role of AZT in DNA methylation. DNA was
extracted with a non-organic extraction kit or phenol-chloroform technique. Genomic
incorporation was determined via anti-AZT radioimmunoassay. Methylation was
examined using restriction enzymes. F or cells exposed to AZT for increasing times, we
found increasing genomic incorporation, but inconclusive methylation results. For the
cells that were treated with increasing concentrations of AZT, we found more
incorporation at the highest concentration. The methylation study of these cells showed a
positive correlation between methylation and AZT incorporation. More AZT is thus
incorporated into DNA with increased dosage and longer exposure. With increasing
incorporation, AZT also induces increasing methylation. Careful examination of these
effects in consideration of human treatments would seem appropriate.
Description
vi, 26 p.
Citation
Publisher
Kalamazoo College
License
U.S. copyright laws protect this material. Commercial use or distribution of this material is not permitted without prior written permission of the copyright holder.