nitrogen mustard


OTHER NAMES:
mechloroethamine


ABBREVIATIONS:
NH2


DESCRIPTION: The nitrogen mustards are cytotoxic chemotherapy agents similar to mustard gas.
Nitrogen mustards (NMs) form cyclic aminium ions (aziridinium rings) by intramolecular displacement of the chloride by the amine nitrogen. This azidirium group then alkylates DNA by attacking the N-7 nucleophilic center on the guanine base. A second attack after the displacement of the second chlorine forms the second alkylation step that results in the formation of interstrand cross-links (ICLs) as it was shown in the early 1960s. At that time it was proposed that the ICLs were formed between N-7 atom of guanine residue in a 5’-d(GC) sequence.[4][5] These kind of lesion are highly cytotoxic, since they block fundamental metabolic processes such as replication and transcription.
The strong cytotoxic effect caused by the formation of ICLs is what makes NMs an effective chemotherapeutic agent. Other compounds used in cancer chemotherapy that have the ability to form ICLs are cisplatin, mitomycin C, carmustine, psoralen.

DNA DAMAGES:
intErstrand crosslinks (ICLs)
intrAstrand crosslink


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NAME STRUCTURE PROTEINS DNA DAMAGE EFFECT(S) PATHWAY(S) RELATED
intErstrand crosslinks (ICLs) UvrC
UvrB
ERCC5 (XPG)
ERCC4 (XPF)
MUS81
EME1
ERCC1
SLX4
SLX1A
SLX1B
TOP3A
cell cycle arrest
DNA backbone distortion
mutagenesis
stalled replication fork
Fanconi anemia (FA) pathway
nucleotide excision repair (NER)
prokaryotic (SOS) response
homologous recombination (HR)
DNA replication
intrAstrand crosslink UvrC
UvrB
ERCC5 (XPG)
ERCC4 (XPF)
cell cycle arrest
DNA backbone distortion
stalled replication fork
Fanconi anemia (FA) pathway
nucleotide excision repair (NER)
prokaryotic (SOS) response

Last modification date: Oct. 12, 2011