Please use this identifier to cite or link to this item: http://hdl.handle.net/2381/15973
Title: Further development of 32P-postlabeling for the detection of alkylphosphotriesters: evidence for the long-term nonrandom persistence of ethyl-phosphotriester adducts in vivo.
Authors: Le Pla RC
Guichard, Y
Bowman, KJ
Gaskell, M
Farmer, PB
Jones, GD
First Published: Nov-2004
Citation: CHEM RES TOXICOL, 2004, 17 (11), pp. 1491-1500
Abstract: DNA phosphate oxygens are sites for alkylation leading to phosphotriester adducts (PTEs). PTEs are reported to be both abundant and persistent and so may serve as long-term markers of genotoxicity. Previously, we reported a 32P-postlabeling assay for the specific detection of PTEs plus identification of nucleosides located 5' to PTEs. Using this, we demonstrated the nonrandom nature of ethyl-PTEs (Et-PTEs) in vivo, these results being suggestive of either the nonrandom formation of Et-PTEs in vivo or sequence specific Et-PTE repair. Presently, we report the further development and validation of the 32P-postlabeling assay, to permit the more straightforward determination of nucleosides 5' to PTEs and, using this, have investigated the long-term persistence of PTEs in vivo. Analysis of liver DNA of mice treated in vivo with N-nitrosodiethylamine reveals an initial decline in the level of Et-PTEs (t1/2<24 h) as well as their nonrandom persistence for the duration of the time course, with approximately 37 and approximately 15% of the initial Et-PTEs remaining 4 and 56 days after treatment, respectively. From this, we conclude that Et-PTEs are suitable as long-term markers of genotoxic exposure and that putative PTE repair is not responsible for their nonrandom manifestation. However, the possibility of active repair contributing to the initial decline of Et-PTEs is considered.
DOI Link: 10.1021/tx049798g
ISSN: 0893-228X
Links: http://hdl.handle.net/2381/15973
Type: Journal Article
Appears in Collections:Published Articles, Dept. of Cancer Studies and Molecular Medicine

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