Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.4.2.8 (hypoxanthine-guanine phosphoribosyltransferase)
 2,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Little is known at the molecular level concerning the genotoxic effects following the acute exposure of eukaryotic cells to low concentrations of lead (II) or mercury (II). There have been conflicting reports concerning the mutagenic potential of these heavy metals, and there have not been any studies performed to determine the molecular mechanism(s) by which these metals are mutagenic. The Chinese hamster ovary cell line, AS52, contains a stably integrated single functional copy of the Escherichia coli xanthine-guanine phosphoribosyltransferase (gpt) gene. Mutations in the gpt gene confer resistance to 6-thioguanine (TG). There was little effect on viability, as measured by relative cloning efficiency, of AS52 cells exposed to lead (II) or mercury (II) up to concentrations of 0.5 microM and 0.3 microM, respectively. However, higher concentrations of the metals caused a significant increase in cell death. There was also a dose-dependent increase in the isolation of mutants resistant to TG in treated cells when compared to non-treated controls. Concentrations of the metals as low as 0.1 microM caused a significant increase in the number of mutants resistant to TG when compared to the number of spontaneous mutants obtained in nontreated controls. While the molecular mechanism(s) by which lead and mercury (II) are genotoxic is unknown, the results of this study demonstrate that low concentrations of lead (II) and mercury (II) are mutagenic in eukaryotic cells.
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PMID:Mutagenesis of AS52 cells by low concentrations of lead(II) and mercury(II) 862 45

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