DNA Alkylation Damage by Nitrosamines and Relevant DNA Repair Pathways.
AAG
ALKBH
BER
DNA alkylation
DNA damage
DNA repair
MGMT
N-nitrosamines
N-nitroso compounds
NER
TLS
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
28 Feb 2023
28 Feb 2023
Historique:
received:
19
01
2023
revised:
17
02
2023
accepted:
24
02
2023
entrez:
11
3
2023
pubmed:
12
3
2023
medline:
15
3
2023
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 36902118
pii: ijms24054684
doi: 10.3390/ijms24054684
pmc: PMC10003415
pii:
doi:
Substances chimiques
Nitrosamines
0
Alkylating Agents
0
DNA Adducts
0
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Deutsche Forschungsgemeinschaft
ID : FA 1034/3-1
Organisme : Deutsche Forschungsgemeinschaft
ID : FA 1034/3-3
Organisme : Deutsche Forschungsgemeinschaft
ID : CH 665/8-1
Organisme : Deutsche Forschungsgemeinschaft
ID : SFB 1361/2 TP 05
Organisme : European Medicines Agency
ID : specific contract no.01 FWC EMA/2020/46/TDA/ L1.02
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