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)

We have investigated the mutagenicity of oxidative DNA damage induced in V79 Chinese hamster lung fibroblast, and measured 8-hydroxydeoxyguanosine (8OHdG) levels as an indicator of this damage. A hydroxyl radical generator, N,N'-bis(2-hydroxyperoxy-2-methoxyethyl)-1,4,5,8-naphthalene-tetra -carboxylic-diimide (NP-III), induced 8OHdG in V79 upon irradiation with 366 nm ultraviolet light (UV) for 15 min. 8OHdG was determined by HPLC with electrochemical detection after anaerobic sample processing. The 8OHdG level in the cells treated without NP-III was 0.49 per 10(5) dG, whereas levels in the cells treated with 5, 10 or 20 microM NP-III and UV irradiation were 1.84, 4.06 or 6.95 per 10(5) dG, respectively. The 8OHdG induced by 20 microM NP-III with UV irradiation decreased rapidly, and the half-life of the induced 8OHdG was approximately 6 h. NP-III with UV irradiation also induced DNA strand breaks in all cells uniformly, as determined by single cell gel assay. Mutant frequencies at the hypoxanthine-guanine phosphoribosyltransferase (hprt) locus in V79 were determined as the number of 6-thioguanine-resistant cells per 10(6) cells. Mutant frequency of the cells without NP-III was 8.0, and frequencies of the cells treated with 5, 10 or 20 microM NP-III and UV irradiation were 14.9, 20.6 or 24.7 respectively. Treatment with 20 microM NP-III and UV irradiation decreased the cell number, determined 3 days after the treatment, to 20.8%. These findings indicate that acutely induced oxidative DNA damage including mutagenic 8OHdG is only weakly mutagenic in V79.
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PMID:Mutagenicity of oxidative DNA damage in Chinese hamster V79 cells. 939 1

DNA damage induced by reactive oxygen species (ROS) seems to play an important role in the induction of mutations and cancer. We have recently shown that hyperbaric oxygen (HBO) treatment of volunteers (i.e., exposure to 100% oxygen at a pressure of 2.5 ATA) induces DNA damage detected in leukocytes with the comet assay. Using formamidopyrimidine-DNA glycosylase (FPG protein) we provided indirect evidence for the induction of oxidative DNA base damage. We now comparatively evaluated FPG-sensitive sites with the comet assay and 7,8-dihydro-8-oxo-deoxyguanosine (8-OHdG) with HPLC analysis after a single HBO. As 8-OHguanine (8-OHgua) is one of the major DNA modifications induced by ROS and a pre-mutagenic lesion, we looked for HBO-induced mutations at the HPRT locus with the T cell cloning test. We also determined the genotypes for glutathione transferases (GST) and tested a possible influence of the GSTM1 and GSTT1 genotypes on the sensitivity of subjects against HBO-induced genotoxicity. Our results indicate that despite a clear induction of FPG-sensitive sites no increased levels of 8-OHdG and no induction of HPRT mutations was detected in lymphocytes after HBO. Furthermore, the DNA effects in the comet assay and the mutant frequencies in the HPRT test seem to be unrelated to the GST genotypes of the test subjects.
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PMID:Analysis of oxidative DNA damage and HPRT mutations in humans after hyperbaric oxygen treatment. 1063