Please use this identifier to cite or link to this item:
http://doi.org/10.25358/openscience-9336
Authors: | Fahrer, Jörg Christmann, Markus |
Title: | DNA alkylation damage by nitrosamines and relevant DNA repair pathways |
Online publication date: | 8-Aug-2023 |
Year of first publication: | 2023 |
Language: | english |
Abstract: | Nitrosamines occur widespread in food, drinking water, cosmetics, as well as tobacco smoke and can arise endogenously. More recently, nitrosamines have been detected as impurities in various drugs. This is of particular concern as nitrosamines are alkylating agents that are genotoxic and carcinogenic. We first summarize the current knowledge on the different sources and chemical nature of alkylating agents with a focus on relevant nitrosamines. Subsequently, we present the major DNA alkylation adducts induced by nitrosamines upon their metabolic activation by CYP450 monooxygenases. We then describe the DNA repair pathways engaged by the various DNA alkylation adducts, which include base excision repair, direct damage reversal by MGMT and ALKBH, as well as nucleotide excision repair. Their roles in the protection against the genotoxic and carcinogenic effects of nitrosamines are highlighted. Finally, we address DNA translesion synthesis as a DNA damage tolerance mechanism relevant to DNA alkylation adducts. |
DDC: | 610 Medizin 610 Medical sciences |
Institution: | Johannes Gutenberg-Universität Mainz |
Department: | FB 04 Medizin |
Place: | Mainz |
ROR: | https://ror.org/023b0x485 |
DOI: | http://doi.org/10.25358/openscience-9336 |
Version: | Published version |
Publication type: | Zeitschriftenaufsatz |
Document type specification: | Scientific article |
License: | CC BY |
Information on rights of use: | https://creativecommons.org/licenses/by/4.0/ |
Journal: | International journal of molecular sciences 24 5 |
Pages or article number: | 4684 |
Publisher: | MDPI |
Publisher place: | Basel |
Issue date: | 2023 |
ISSN: | 1422-0067 |
Publisher DOI: | 10.3390/ijms24054684 |
Appears in collections: | DFG-491381577-G |
Files in This Item:
File | Description | Size | Format | ||
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![]() | dna_alkylation_damage_by_nitr-20230802113742518.pdf | 4.66 MB | Adobe PDF | View/Open |