![](/images/graphics-bg.png)
Elevated Levels of DNA Strand Breaks Induced by a Base Analog in the Human Cell Line with the P32T ITPA Variant
Joint Authors
Pavlov, Youri I.
Waisertreiger, Irina S.-R.
Randazzo, James
Menezes, Miriam R.
Source
Issue
Vol. 2010, Issue 2010 (31 Dec. 2010), pp.1-11, 11 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2010-09-26
Country of Publication
Egypt
No. of Pages
11
Main Subjects
Abstract EN
Base analogs are powerful antimetabolites and dangerous mutagens generated endogenously by oxidative stress, inflammation, and aberrant nucleotide biosynthesis.
Human inosine triphosphate pyrophosphatase (ITPA) hydrolyzes triphosphates of noncanonical purine bases (i.e., ITP, dITP, XTP, dXTP, or their mimic: 6-hydroxyaminopurine (HAP) deoxynucleoside triphosphate) and thus regulates nucleotide pools and protects cells from DNA damage.
We demonstrate that the model purine base analog HAP induces DNA breaks in human cells and leads to elevation of levels of ITPA.
A human polymorphic allele of the ITPA, 94C->A encodes for the enzyme with a P32T amino-acid change and leads to accumulation of nonhydrolyzed ITP.
The polymorphism has been associated with adverse reaction to purine base-analog drugs.
The level of both spontaneous and HAP-induced DNA breaks is elevated in the cell line with the ITPA P32T variant.
The results suggested that human ITPA plays a pivotal role in the protection of DNA from noncanonical purine base analogs.
American Psychological Association (APA)
Waisertreiger, Irina S.-R.& Menezes, Miriam R.& Randazzo, James& Pavlov, Youri I.. 2010. Elevated Levels of DNA Strand Breaks Induced by a Base Analog in the Human Cell Line with the P32T ITPA Variant. Journal of Nucleic Acids،Vol. 2010, no. 2010, pp.1-11.
https://search.emarefa.net/detail/BIM-505089
Modern Language Association (MLA)
Waisertreiger, Irina S.-R.…[et al.]. Elevated Levels of DNA Strand Breaks Induced by a Base Analog in the Human Cell Line with the P32T ITPA Variant. Journal of Nucleic Acids No. 2010 (2010), pp.1-11.
https://search.emarefa.net/detail/BIM-505089
American Medical Association (AMA)
Waisertreiger, Irina S.-R.& Menezes, Miriam R.& Randazzo, James& Pavlov, Youri I.. Elevated Levels of DNA Strand Breaks Induced by a Base Analog in the Human Cell Line with the P32T ITPA Variant. Journal of Nucleic Acids. 2010. Vol. 2010, no. 2010, pp.1-11.
https://search.emarefa.net/detail/BIM-505089
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-505089