Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P00492 (hypoxanthine-guanine phosphoribosyltransferase)
 2,385 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The fusion of thioglycollate-elicited peritoneal macrophages from the lipopolysaccharide (LPS)-nonresponsive C3H/HeJ mouse strain to a hypoxanthine phosphoribosyltransferase (HPRT)-negative variant of the murine macrophage cell line P388D1 has resulted in the derivation of eight hybrid clones following HAT selection. Propidium-Iodide staining followed by flow cytometry has demonstrated that the DNA content of the hybrids represents the sum of the parents. Codominant expression of class I antigens from both parental haplotypes is observed in the hybrids. While class II antigens are inducible following a 72-hr induction with gamma interferon-containing supernatants, the amount of each haplotype varies between clones. These hybrids demonstrate Fc-mediated erythrophagocytosis in contrast to P388D1. In distinction to the C3H/HeJ primary peritoneal-macrophage parent, LPS treatment of the hybrids results in the increased release of both interleukin-1 (IL-1) and cachectin/tumor necrosis factor (TNF) into culture supernatants. Therefore, cell fusion has resulted in the stable restoration of the LPS-responsive phenotype in C3H/HeJ macrophage hybrids. These macrophage hybrids should serve as useful models in understanding the regulation of macrophage effector functions in response to environmental stimuli.
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PMID:Restoration of the lipopolysaccharide-responsive phenotype in C3H/HeJ peritoneal macrophage-P388D1 cell hybrids. 325 49

To better understand the mechanisms through which persistent infections/inflammation increase cancer risks, we assessed the potential genotoxic properties of NO produced by macrophages. We recently showed that mouse macrophage RAW264.7 cells were capable of resuming exponential growth after stimulation for NO production by interferon-gamma (IFN-gamma) and/or lipopolysaccharide. Here, we report that increases in mutant fraction (MF) in the endogenous, X-linked, hprt gene of the cells are associated with NO exposure. Cells stimulated with 100 units/ml IFN-gamma continuously for 14 and 23 days produced a total of 9.8 and 14 micromol of NO per 10(7) cells, respectively. MFs in the hprt gene of NO-producing cells were 16.6 and 31.3 x 10(-5), respectively, compared with 2.2 and 2.5 x 10(-5) in untreated cells. Addition of an NO synthase inhibitor, N-monomethyl-L-arginine, to the culture medium decreased NO production and MF by 90% and 85%, respectively. Reverse transcription-PCR and DNA sequencing revealed that NO-associated hprt mutations did not differ significantly from those arising spontaneously, with the exception that certain small deletions/insertions and multiple exon deletions were observed only in the former. MF also increased significantly in cells stimulated for only 4 days with lipopolysaccharide plus IFN-gamma for higher rates of NO production. The types and proportion of hprt mutations induced under these conditions were strikingly similar to those associated with long-term NO exposure. These results indicate that NO exposure results in gene mutations in RAW264.7 cells through mechanisms yet to be identified and may also contribute to spontaneous mutagenesis.
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PMID:Mutagenesis associated with nitric oxide production in macrophages. 965 79