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

We have investigated the ability of the naturally occurring plant essence vanillin (3-methoxy-4-hydroxybenzaldehyde) to inhibit mutation at the CD59 locus on human chromosome 11 by hydrogen peroxide, N-methyl-N-nitrosoguanidine, mitomycin C and (137)Cs gamma-radiation in human-hamster hybrid A(L) cells. Previous studies using vanillin have suggested that it can inhibit chromosome aberrations induced by hydrogen peroxide and mitomycin C, as well as inhibiting X-ray- and UV-induced mutations at the hprt locus. Other studies with vanillin have shown that it can increase both the toxicity and mutagenicity of ethyl methane sulfonate and increase the induction of sister chromatid exchange by mitomycin C and a variety of other mutagens. The increased sensitivity of the A(L) assay, which is due in part to its ability to detect both small (single locus) and large (multilocus) genetic damage, allows us to measure the effect of vanillin at low doses of mutagen. Vanillin is shown, in these studies, to inhibit mutation induced by hydrogen peroxide, N-methyl-N-nitrosoguanidine and mitomycin C, as well as to enhance the toxicity of these agents. Vanillin had no effect on either toxicity or mutation induced by (137)Cs gamma-radiation. The vanillin-induced potentiation of H(2)O(2) toxicity is shown not to involve inhibition of catalase or glutathione peroxidase. These results show that vanillin is able to inhibit mutation at the CD59 locus and modify toxicity in a mutagen-specific manner. Possible mechanisms to explain the action of vanillin include inhibition of a DNA repair process that leads to the death of potential mutants or enhancement of DNA repair pathways that protect from mutation but create lethal DNA lesions during the repair process.
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PMID:Vanillin (3-methoxy-4-hydroxybenzaldehyde) inhibits mutation induced by hydrogen peroxide, N-methyl-N-nitrosoguanidine and mitomycin C but not (137)Cs gamma-radiation at the CD59 locus in human-hamster hybrid A(L) cells. 1079 12

Phosphatidylinositol glycan-A (PIGA) is a gene that encodes an element required for the first step in glycosylphosphatidylinositol (GPI) anchor assembly. Because PIGA is X-located, a single mutation is sufficient to abolish cell surface GPI-anchored protein expression. In this study, we investigated whether mutation of the PIGA gene could be exploited to identify mutator (Mut) phenotypes in cancer. We examined eight Mut colon cancer lines and four non-Mut colon cancers as controls. In every case, flow cytometric analyses of cells sorted for low fluorescence after staining for GPI-linked CD59 and CD55 revealed negative peaks in the Mut lines but not in the controls. Single cell cloning of purged and sorted GPI-anchor- HCT116 cells and sequencing of the PIGA gene in each clone uniformly showed mutations. Pretreatment of the Mut lines with anti-CD55 or anti-CD59 antibodies and complement or with the GPI-anchor-reactive bacterial toxin aerolysin enriched for the GPI-anchor- populations. Expansion of purged GPI-anchor+ cells in the Mut lines and analyses using aerolysin in conjunction with flow cytometry yielded PIGA gene mutation frequencies of 10(-5) to 10(-4), values similar to the mutation frequencies of the hprt gene. This novel approach allows for the detection of as yet undescribed repair or replication defects and in addition to its considerably greater ease of use than existing techniques and in principle would not require the production of cell lines.
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PMID:Glycophosphatidylinositol-anchored protein deficiency as a marker of mutator phenotypes in cancer. 1121 64