Induction of 8-oxo-dGTPase activity in human lymphoid cells and normal fibroblasts by oxidative stress.
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Induction of 8-oxo-dGTPase activity in human lymphoid cells and normal fibroblasts by oxidative stress. / Meyer, F; Fiala, E; Westendorf, Johannes.
In: TOXICOLOGY, Vol. 146, No. 2-3, 2-3, 2000, p. 83-92.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Induction of 8-oxo-dGTPase activity in human lymphoid cells and normal fibroblasts by oxidative stress.
AU - Meyer, F
AU - Fiala, E
AU - Westendorf, Johannes
PY - 2000
Y1 - 2000
N2 - 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.
AB - 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.
M3 - SCORING: Zeitschriftenaufsatz
VL - 146
SP - 83
EP - 92
JO - TOXICOLOGY
JF - TOXICOLOGY
SN - 0300-483X
IS - 2-3
M1 - 2-3
ER -