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)

Mercury is a highly deleterious environmental pollutant, with recognized mutagenic and teratogenic effects. Given this, we evaluated the changes induced in vitro by two mercury compounds (mercury chloride--MC--and methyl mercuric chloride--MMC) on the genetic) material of a human lymphoblastoid cell line (TK6) on the basis of both the frequency of mutations at the hprt locus, and the number of chromosomic anomalies. The frequencies of HPRT- mutants in the TK6 cell line following exposure to the mercury compounds are inconclusive with regard to a mutagenic effect. However, both mercury compounds exhibit a clear cytotoxic effect, which increases with dosage. There was also no statistically significant increase in the frequency of chromosomic bleakage or gaps, nor in the number of cells with chromosomic alterations in the lymphoblastoid line. Nevertheless, MMC did provoke a marked reduction in the frequency of mitosis, both on its own and in combination with MC.
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PMID:Genotoxic effects of mercury on in vitro cultures of human cells. 1053 Mar 33

We conducted the recombination and sister chromatid exchange (SCE) assays with five chemicals (hydroxyurea (HU), resveratrol, 4-hydroxy-trans-stilbene, 3-hydroxy-trans-stilbene, and mitomycin C) in Chinese hamster cell line SPD8/V79 to confirm directly that SCE is a result of homologous recombination (HR). SPD8 has a partial duplication in exon 7 of the endogenous hprt gene and can revert to wild type by homologous recombination. All chemicals were positive in both assays except for 3-hydroxy-trans-stilbene, which was negative in both. HU, resveratrol, and 4-hydroxy-trans-stilbene were scavengers of the tyrosyl free radical of the R2 subunit of mammalian ribonucleotide reductase. Tyrosyl free radical scavengers disturb normal DNA replication, causing replication fork arrest. Mitomycin C is a DNA cross-linking agent that also causes replication fork arrest. The present study suggests that replication fork arrest, which is similar to the early phases of HR, leads to a high frequency of recombination, resulting in SCEs. The findings show that SCE may be mediated by HR.
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PMID:Correlation of sister chromatid exchange formation through homologous recombination with ribonucleotide reductase inhibition. 1501 4