Disease relevance of NSC 28172

• The level of 5-chlorouracil was 10-fold higher in atherosclerotic aortic tissue obtained during vascular surgery than in normal aortic tissue, suggesting that halogenated nucleobases produced by macrophages might contribute to atherogenesis [1].
• A marked improvement in selectivity was noted for the 5-chlorouracil derivatives of 2,3-dideoxyribofuranose, 3-azido-2,3-dideoxyribofuranose, and 3-fluoro-2,3-dideoxyribofuranose, mainly due to decreased toxicity of the compounds for the host cells [2].
• Several 5-chlorouracil and 5-chlorocytosine beta-L-dideoxynucleosides were stereospecifically synthesized and their activities against human immunodeficiency virus (HIV) and hepatitis B virus (HBV) were examined in cell culture [3].

High impact information on NSC 28172

• Myeloperoxidase generates 5-chlorouracil in human atherosclerotic tissue: a potential pathway for somatic mutagenesis by macrophages [1].
• Because 5-chlorouracil can be incorporated into nuclear DNA, our observations raise the possibility that halogenation reactions initiated by phagocytes provide one pathway for mutagenesis, phenotypic modulation, and cytotoxicity during atherogenesis [1].
• In the current studies, we demonstrate that myeloperoxidase produced by human macrophages differentiated in the presence of granulocyte macrophage colony-stimulating factor generates 5-chlorouracil, a mutagenic thymine analog [1].
• In this study, we demonstrate that human neutrophils use myeloperoxidase to oxidize uracil to 5-chlorouracil in vitro [4].
• 5-Chlorouracil, a marker of DNA damage from hypochlorous acid during inflammation. A gas chromatography-mass spectrometry assay [5].

Biological context of NSC 28172

• Following oligonucleotide synthesis and deprotection, only trace amounts of the deamination product 5-chlorouracil can be detected by enzymatic cleavage of duplex oligonucleotides with the mispaired uracil glycosylase, MUG [6].
• The genetic toxicology of 5-fluoropyrimidines and 5-chlorouracil [7].

Anatomical context of NSC 28172

• Environmental pollutant 5-chlorouracil is incorporated in mouse liver and testes DNA [8].

Associations of NSC 28172 with other chemical compounds

• Because 5-chlorouracil and 5-bromouracil can be incorporated into nuclear DNA, and these thymine analogs are well known mutagens, our observations raise the possibility that halogenation reactions initiated by phagocytes provide one pathway for mutagenesis and cytotoxicity at sites of inflammation [4].

Gene context of NSC 28172

• Cytidine deaminase from mouse kidney converted CDC into CDU; thymidine phosphorylase converted CDU into 5-chlorouracil (5-CU) [9].
• Introduction of an N-substituted aminomethyl side chain at the 6-position of 5-chlorouracil has improved water solubility and enhanced inhibitory activity compared with the known TP inhibitor, 6-amino-5-chlorouracil [10].
• The space group is P21/c, with a equals 8.450(6), b equals 6.842(3), c equals 11.072(16) angstrom, beta equals 123.53(19) degrees for 5-chlorouracil, and a equals 8.598(3), b equals 6.886(1), c equals 11.417(5) angstrom, beta equals 123.93(3) degrees for 5-bromouracil [11].

Analytical, diagnostic and therapeutic context of NSC 28172

• Retrodialysis calibration using 5-chlorouracil (5-CU) was performed in conjunction with on-line HPLC analysis [12].

References