𝔖 Bobbio Scriptorium
✦   LIBER   ✦

Program 2000 Environmental Mutagen Society Annual Meeting April 8–April 13, 2000 New Orleans, LA. Jim Tucker, Program Chair

Publisher
John Wiley and Sons
Year
2000
Tongue
English
Weight
244 KB
Volume
35
Category
Article
ISSN
0893-6692

No coin nor oath required. For personal study only.

✦ Synopsis

Oxidative DNA damage is a function of intracellular factors and the delivery mode of reactive oxygen species (ROS) into the cell. In the present study, hydrogen peroxide (H2O2) and nitric oxide (NO) were shown to induce cytotoxicity and mutation in the transgenic Chinese hamster G12 cells. Delivery of H2O2 and NO was optimized using glucose/glucose oxidase (GO) and spermine NONOate (SperNO), respectively. GO-cytotoxicity (24 mUnits) increased with treatment time; a 15-min incubation yielded ~50% survival, and a 1-hr incubation induced maximal cell killing (>95%). GO induced an increase in mutant frequency (MF) from 40 to 200x10 6 for treatment durations of 45 min (20% survival). SperNO induced toxicity at doses of 0.5 -12 µM, survival rate at 12 µM was ~25%. Induced MF by SperNO (10 µM) was 140x10 6 vs. 55x10

6 in the control.

Based on previous studies in Salmonella that demonstrated synergism in H2O2-and NOinduced mutagenesis, the ROS were investigated for synergism in G12 cells. Cells exposed to SperNO (5 µM ) then GO treatment of 0, 15, 30, 45, and 60 min, showed synergism, especially at the 30-min incubation time.

The production of more potent mutagens/cytotoxins such as peroxynitrite may contribute to the observed synergism. In contrast, cells exposed to various doses of SperNO and one treatment of GO showed no synergism, but rather a slight drop in MF from 43 to 30x10 6 . The Fenton reaction is known to be influenced negatively by NO under certain treatment conditions. These findings confirm the complexity of mechanisms governing oxidative damage and repair in mammalian cells.

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