TY - JOUR
T1 - DT-diaphorase protects against menadione-induced oxidative stress
AU - Chiou, Tzeon Jye
AU - Wang, Yu Tai
AU - Tzeng, Woan Fang
N1 - Funding Information:
This work was supported by grant NSC 87-2311-B-030-003 from the National Science Council, Taipei, Taiwan, ROC.
PY - 1999/11
Y1 - 1999/11
N2 - To study the role of DT-diaphorase in menadione-mediated cytotoxicity, menadione-resistant cells were selected from P19 cells by stepwise increasing concentrations of menadione from 10 to 60, 120 or 300 μM without mutagenic pretreatment. Three isolated clones, K60, K120 and K300, were maintained in media containing 60, 120 or 300 μM menadione, respectively. The resistance of these cells to menadione, in order, was: K300>K120>K60>P19 cells. K300 cells were the most resistant. Acquisition of resistance was associated with elevation in DT-diaphorase activity. Pretreatment of the resistant cells with 30 μM dicumarol at 37°C for 30 min sensitized the resistant cells to menadione. When the resistant cells were maintained in the absence of menadione for 28 days, the resistance of K60 and K120 cells was lost. The lower degree of resistance was accompanied by a decrease in DT-diaphorase activity in the revertant cells. However, the resistance and the activity of DT-diaphorase in K300 cells were quite stable in the same period. These results support strongly that DT-diaphorase protects against menadione-induced oxidative stress. Copyright (C) 1999 Elsevier Science Ireland Ltd.
AB - To study the role of DT-diaphorase in menadione-mediated cytotoxicity, menadione-resistant cells were selected from P19 cells by stepwise increasing concentrations of menadione from 10 to 60, 120 or 300 μM without mutagenic pretreatment. Three isolated clones, K60, K120 and K300, were maintained in media containing 60, 120 or 300 μM menadione, respectively. The resistance of these cells to menadione, in order, was: K300>K120>K60>P19 cells. K300 cells were the most resistant. Acquisition of resistance was associated with elevation in DT-diaphorase activity. Pretreatment of the resistant cells with 30 μM dicumarol at 37°C for 30 min sensitized the resistant cells to menadione. When the resistant cells were maintained in the absence of menadione for 28 days, the resistance of K60 and K120 cells was lost. The lower degree of resistance was accompanied by a decrease in DT-diaphorase activity in the revertant cells. However, the resistance and the activity of DT-diaphorase in K300 cells were quite stable in the same period. These results support strongly that DT-diaphorase protects against menadione-induced oxidative stress. Copyright (C) 1999 Elsevier Science Ireland Ltd.
KW - DT-diaphorase
KW - Menadione resistance
KW - Oxidative stress
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U2 - 10.1016/S0300-483X(99)00109-2
DO - 10.1016/S0300-483X(99)00109-2
M3 - Article
C2 - 10614691
AN - SCOPUS:0032695073
SN - 0300-483X
VL - 139
SP - 103
EP - 110
JO - Toxicology
JF - Toxicology
IS - 1-2
ER -