Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.22.1 (DNase II)
 429 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The cellular basis for the enhanced sensitivity to ionising radiation and some DNA damaging chemicals in ataxia-telangiectasia (AT) cells is not clearly understood. Abnormalities in cell-cycle traverse, chromosome stability and DNA synthesis patterns have suggested that a chromatin associated defect may be the primary lesion in AT. This study involves an attempt to define such an anomaly by the use of a vital DNA specific bis-benzimidazole dye (Hoechst 33342) and deoxyribonuclease II as probes for chromatin organisation in intact and permeabilised human cells respectively. Despite similar DNA binding characteristics (determined by flow cytometry) of Ho33342 in normal and AT transformed fibroblasts, the AT cells show: (i) enhanced cell killing and increased accumulation of cells in G2 phase of the cell-cycle [both biological responses being relatively resistant in AT cells to modification by an inhibitor of poly (ADP ribosyl)ation], (ii) no resistance of de novo DNA synthesis to Ho33342-induced inhibition, (iii) elevated levels of slow-rejoining ligand-induced DNA strand-breaks, and (iv) enhanced expression of chromatin regions accessible to an exogenously supplied endonuclease. The results are interpreted on the basis that a chromatin anomaly of enhanced nuclease susceptibility, involving a minor fraction of the genome, may be a controlling factor in the expression of the various in vivo and in vitro characteristics of AT cells.
Carcinogenesis 1984 Oct
PMID:Relationship between a chromatin anomaly in ataxia-telangiectasia cells and enhanced sensitivity to DNA damage. 648 55

BACKGROUND: It has been documented that nitric oxide (NO) donor sodium nitroprusside (SNP) and authentic peroxynitrite are capable of promoting apoptosis in a number of different cell types. Various endonucleases have been proposed as candidates responsible for the internucleosomal cleavage of the genomic DNA observed during apoptosis, but the main effect is attributed to the alkaline-DNases (Mg2+- and caspase-dependent) and acid-DNase. The aim of this study was to examine an in vivo and in vitro possibility for alkaline- and acid-DNases to be activated by SNP and peroxynitrite. RESULTS: The effect on liver tissue alkaline and acid DNase activity together with the markers of tissue and plasma oxidative and nitrosative stress (lipid peroxidation, SH group content, carbonyl groups and nitrotyrosine formation) was investigated in plasma and liver tissue. The activity of liver alkaline DNase increased and that of acid DNase decreased after in vivo treatment with either SNP or peroxynitrite. A difference observed between the in vivo and in vitro effect of oxide donor (i.e., SNP) or peroxynitrite upon alkaline DNase activity existed, and it may be due to the existence of the "inducible" endonuclease. After a spectrophotometric scan analysis of purified DNA, it was documented that both SNP and peroxynitrite induce various DNA modifications (nitroguanine formation being the most important one) whereas DNA fragmentation was not significantly increased. CONCLUSION: Alkaline DNase activation seems to be associated with the programmed destruction of the genome, leading to the fragmentation of damaged DNA sites. Thus, the elimination of damaged cells appears to be a likely factor in prevention against mutation and carcinogenesis.
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PMID:Sodium nitroprusside and peroxynitrite effect on hepatic DNases: an in vitro and in vivo study. 1533 33

The alterations of deoxyribonuclease DNase activity in cancer cells were the basis of the utilization of mixed vitamins C and K3 in a nontoxic, adjuvant cancer therapy. In order to localize exactly the altered activities of DNase in cancer cells, histochemical methods were utilized. The deficiency of alkaline and acid DNase activity appeared to be characteristic for non-necrotic cells of malignant human and animal tumors. This enzymatic deficiency appeared in experimental carcinogenesis before the phenotypic signs of malignancy. Tumor promoters directly reduced the activity of both DNases. The incidence of spontaneous malignant human and animal tumors appeared to be inversely proportional to the intensity of the activity of both DNases in normal cells and tissues from which these tumors were derived. The fact that alkaline and acid DNase activity was reactivated during the spontaneous and therapeutically induced necrosis of cancer cells suggests that this enzymatic deficiency of DNase activity in cancer cells was due to the action of specific inhibitors of DNases. Characteristic variations of serum alkaline DNase activity in positive responders to therapy, examined in more than 800 cancer-bearing patients, may be the basis for the development of a useful test for therapeutic prognosis and for monitoring of cancer bearing patients. Acid DNase was selectively reactivated in malignant tumor cells by vitamin C (sodium ascorbate), whereas alkaline DNase was reactivated by vitamin K3. Joint vitamin C and K3 administration produced in vitro and in vivo tumor growth inhibition, potentiation and sensitization of chemo- and/or radiotherapy and a decrease in the number of metastases in animals with experimental tumors. Joint vitamin C and K3 administration may be considered as a possible new, non-toxic, adjuvant cancer therapy, which can be easily introduced into the classic protocols of clinical cancer therapy without any supplementary risk for patients.
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PMID:Altered deoxyribonuclease activity in cancer cells and its role in non toxic adjuvant cancer therapy with mixed vitamins C and K3. 1903 2