Klaus Becker
Does increase in DNA repair allow "Tolerance-to-Insult" in chemical carcinogenesis? Skin tumor experiments with MGMT-overexpressing mice
Becker, Klaus; Thomas, Adam D.; Kaina, Bernd
Authors
Abstract
Several genotoxicity endpoints have been evaluated to define nonlinear dose-responses for S N 1 and S N 2 alkylating genotoxicants. Dose-response studies acknowledging the process of multistage tumorigenesis are important; however, data pertaining nonlinearity are not yet available. In this communication, the role of DNA repair in the dose-response relationship for benign papillomas was examined using the two-stage skin carcinogenesis protocol. The data obtained with O 6 -methylguanine-DNA methyltransferase (MGMT) overexpressing mice in which papillomas were induced by a single topical treatment with N-methyl-N-nitrosourea (MNU) followed by promotion with 12-O-tetradecanoylphorbol-13-acetate are reported. As MGMT efficiently protects cells from mutations by repairing O 6 -methylguanine, a miscoding lesion induced by MNU, the question whether MGMT is able to nullify carcinogenic lesions to an extent where they would be considered nonhazardous has been addressed. It is shown here that MGMT overexpression significantly protects against, but does not completely nullify, the effect of MNU in tumor initiation. The possible mechanisms involved have also been discussed. Environ. Mol. Mutagen. 55:145-150, 2014. © 2013 Wiley Periodicals, Inc.
Citation
Becker, K., Thomas, A. D., & Kaina, B. (2014). Does increase in DNA repair allow "Tolerance-to-Insult" in chemical carcinogenesis? Skin tumor experiments with MGMT-overexpressing mice. Environmental and Molecular Mutagenesis, 55(2), 145-150. https://doi.org/10.1002/em.21834
Journal Article Type | Article |
---|---|
Acceptance Date | Sep 5, 2013 |
Online Publication Date | Dec 1, 2013 |
Publication Date | Mar 1, 2014 |
Journal | Environmental and Molecular Mutagenesis |
Print ISSN | 0893-6692 |
Electronic ISSN | 1098-2280 |
Publisher | Wiley |
Peer Reviewed | Peer Reviewed |
Volume | 55 |
Issue | 2 |
Pages | 145-150 |
DOI | https://doi.org/10.1002/em.21834 |
Public URL | https://uwe-repository.worktribe.com/output/933411 |
Publisher URL | https://doi.org/10.1002/em.21834 |
You might also like
MicroRNAs and the DNA damage response: How is cell fate determined?
(2021)
Journal Article
MicroRNAs, damage levels, and DNA damage response control
(2021)
Journal Article
Downloadable Citations
About UWE Bristol Research Repository
Administrator e-mail: repository@uwe.ac.uk
This application uses the following open-source libraries:
SheetJS Community Edition
Apache License Version 2.0 (http://www.apache.org/licenses/)
PDF.js
Apache License Version 2.0 (http://www.apache.org/licenses/)
Font Awesome
SIL OFL 1.1 (http://scripts.sil.org/OFL)
MIT License (http://opensource.org/licenses/mit-license.html)
CC BY 3.0 ( http://creativecommons.org/licenses/by/3.0/)
Powered by Worktribe © 2024
Advanced Search