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

Chinese hamster ovary (CHO) cells were exposed to thermal and epithermal neutrons, and the occurrence of mutations at the HPRT locus was investigated. The Kyoto University Research Reactor (KUR), which has been improved for use in neutron capture therapy, was the neutron source. Neutron energy spectra ranging from nearly pure thermal to epithermal can be chosen using the spectrum shifters and thermal neutron filters. To determine mutant frequency and cell survival, cells were irradiated with thermal and epithermal neutrons under three conditions: thermal neutron mode, mixed mode with thermal and epithermal neutrons, and epithermal neutron mode. The mutagenicity was different among the three irradiation modes, with the epithermal neutrons showing a mutation frequency about 5-fold that of the thermal neutrons and about 1.5-fold that of the mixed mode. In the thermal neutron and mixed mode, boron did not significantly increase the frequency of the mutants at the same dose. Therefore, the effect of boron as used in boron neutron capture therapy (BNCT) is quantitatively minimal in terms of mutation induction. Over 300 independent neutron-induced mutant clones were isolated from 12 experiments. The molecular structure of HPRT mutations was determined by analysis of all nine exons by multiplex polymerase chain reaction. In the thermal neutron and mixed modes, total and partial deletions were dominant and the fraction of total deletions was increased in the presence of boron. In the epithermal neutron mode, more than half of the mutations observed were total deletions. Our results suggest that there are clear differences between thermal and epithermal neutron beams in their mutagenicity and in the structural pattern of the mutants that they induce. Mapping of deletion breakpoints of 173 partial-deletion mutants showed that regions of introns 3-4, 7/8-9 and 9-0 are sensitive to the induction of mutants by neutron irradiation.
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PMID:Molecular structural analysis of HPRT mutations induced by thermal and epithermal neutrons in Chinese hamster ovary cells. 1095 38

We investigated the biological effects of the long-lived radicals induced following neutron irradiation. It has been reported that radiation-induced long-lived radicals were scavenged by post-irradiation treatment of ascorbic acid (Koyama, 1998). We studied the effects of ascorbic acid acting as a long-lived radical scavenger on cell killing and mutagenicity in Chinese hamster ovary cells against thermal neutrons produced at the Kyoto University Research reactor. Ascorbic acid was added to cells 30 min after neutron irradiation and removed 150 min after irradiation. The biological end point of cell survival was measured by colony formation assay. The mutagenicity was measured by the mutant frequency in the HPRT locus. The post-irradiation treatment of ascorbic acid did not alter the cell killing effect of neutron radiation. However, the mutagenicity was decreased, especially when the cells were irradiated with boron. Our results suggested that ascorbic acid scavenged long-lived radicals effectively and caused apparent protective effects against mutagenicity of boron neutron capture therapy.
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PMID:Ascorbic acid reduced mutagenicity at the HPRT locus in CHO cells against thermal neutron radiation. 1530 70

To investigate bystander mutagenic effects induced by alpha particles during boron neutron capture therapy (BNCT), we mixed cells that were electroporated with borocaptate sodium (BSH), which led to the accumulation of (10)B inside the cells, with cells that did not contain the boron compound. BSH-containing cells were irradiated with alpha particles produced by the (10)B(n,alpha)(7)Li reaction, whereas cells without boron were only affected by the (1)H(n,gamma)(2)H and (14)N(n,rho)(14)C reactions. The frequency of mutations induced in the hypoxanthine-guanine phosphoribosyltransferase (HPRT) locus was examined in Chinese hamster ovary (CHO) cells irradiated with neutrons (Kyoto University Research Reactor: 5 MW). Neutron irradiation of 1:1 mixtures of cells with and without BSH resulted in a survival fraction of 0.1, and the cells that did not contain BSH made up 99.4% of the surviving cell population. Using multiplex polymerase chain reactions (PCRs), molecular structural analysis indicated that most of the mutations induced by the bystander effect were point mutations and that the frequencies of total and partial deletions induced by the bystander effect were lower than those resulting from the alpha particles produced by the (10)B(n,alpha)(7)Li reaction or the neutron beam from the (1)H(n,gamma)(2)H and (14)N(n,rho)(14)C reactions. The types of point mutations induced by the BNCT bystander effect were analyzed by cloning and sequencing methods. These mutations were comprised of 65.5% base substitutions, 27.5% deletions, and 7.0% insertions. Sequence analysis of base substitutions showed that transversions and transitions occurred in 64.7% and 35.3% of cases, respectively. G:C-->T:A transversion induced by 8-oxo-guanine in DNA occurred in 5.9% of base substitution mutants in the BNCT bystander group. The characteristic mutations seen in this group, induced by BNCT alpha particles, differed from those typical of gamma ray radiation.
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PMID:Bystander effect-induced mutagenicity in HPRT locus of CHO cells following BNCT neutron irradiation: characteristics of point mutations by sequence analysis. 1937 34