Induction of 8-oxo-dGTPase activity in human lymphoid cells and normal fibroblasts by oxidative stress.
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| Abstract |
The pre-mutagen 8-Oxo-2'-deoxyguanosine-5'-triphosphate (8-oxo-dGTP) is formed during normal cellular metabolism and its incorporation into DNA leads to transversion mutations. Human cells possess the hMTH-1 gene encoding the enzyme 8-oxo-dGTPase, which catalyzes the hydrolysis of 8-oxo-dGTP to the corresponding 8-oxo-dGMP, preventing mutations. To elucidate the involvement of 8-oxo-dGTPase in carcinogenesis, we studied hMTH-1 gene expression and enzyme activity in response to oxidative stress to human skin fibroblasts and Jurkat cells. In fibroblasts, ranges from 0 to 100 microM H(2)O(2) caused a 2-fold induction of hMTH-1-mRNA expression and a 3-fold induction of enzyme activity. A 1.7-fold induction of mRNA expression and a 3.5-fold induction of enzyme activity was obtained in Jurkat cells after treatment ranging from 0 to 300 microM H(2)O(2). Cytotoxic concentrations of hydrogen peroxide lead to an almost complete loss of enzyme activity and an inhibition of hMTH-1 mRNA expression. Induction of hMTH-1 gene expression was prevented by addition of actinomycin D and cycloheximide. These data indicate the inducibility of the hMTH-1 gene expression and enzyme activity by prooxidative molecules, such as hydrogen peroxide. These parameters can thus be used as a marker of oxidative stress.
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| Authors | F Meyer, E Fiala, J Westendorf |
| Journal | Toxicology (Toxicology) Vol. 146 Issue 2-3 Pg. 83-92 (May 05 2000) ISSN: 0300-483X [Print] Ireland |
| PMID | 10814841 (Publication Type: Journal Article) |
| Chemical References |
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