Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.30.2 (endonuclease)
 18,621 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Only two DNA repair enzymes, DNA polymerase beta and O6-methylguanine-DNA methyltransferase, have been shown to be inducible in mammalian cells by genotoxic agents. We show here that crocidolite asbestos induces the DNA repair enzyme, apurinic/apyrimidinic (AP)-endonuclease, in isolated mesothelial cells, the progenitor cells of malignant mesothelioma. Asbestos at nontoxic concentrations of 1.25 and 2.5 microg/cm2 significantly increased AP-endonuclease mRNA and protein levels as well as enzyme activity (P < 0.05) in a dose-dependent manner in rat pleural mesothelial cells. These increases were persistent from 24 to 72 h after initial exposure to fibers. Changes were not observed with glass beads, a noncarcinogenic particle. Confocal scanning laser microscopy showed that AP-endonuclease was primarily localized in the nucleus but also in mitochondria. Our data are the first to demonstrate the inducibility of AP-endonuclease by a human class I carcinogen associated with oxidant stress in normal cells of the lung.
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PMID:Asbestos increases mammalian AP-endonuclease gene expression, protein levels, and enzyme activity in mesothelial cells. 944 89

Asbestos and man-made-mineral fibers are known to increase one type of oxidative DNA damage, 8-hydroxyguanine (8-OH-(Gua), in vitro. In this study, we analyzed the 8-OH-Gua level in DNA and its repair activity after a single intratracheal instillation of fibers (crocidolite or glass) or saline to Syrian hamsters or Wistar rats. The 8-OH-Gua level was measured with a high-performance liquid chromatography-electrochemical detector (HPLC-ECD) system. The 8-OH-Gua repair enzyme activity was determined with an endonuclease nicking assay using a 32P-labeled or fluorescently labeled 22mer DNA that contains 8-OH-Gua at a specific position. A significant increase in the 8-OH-Gua level in the lung DNA was observed 1 day after the exposure to crocidolite, as compared to the saline control. The repair activity was increased significantly at 7 days. On the other hand, after exposure to glass fibers, little or no increase of these carcinogenicity indicators was detected. These assays of 8-OH-Gua and its repair activity in short-term animal experiments will be useful for evaluating the carcinogenicity of fibers. This is the first report of the increase of 8-OH-Gua and its repair activity in the animal lung after the instillation of asbestos fibers.
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PMID:Increased 8-hydroxyguanine in DNA and its repair activity in hamster and rat lung after intratracheal instillation of crocidolite asbestos. 1039 Oct 89