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DNA FRAGMENTATION CAUSED BY REACTIVE OXYGEN SPECIES IN VIVO WITHOUT INCREASED 8-OH-dG CONTENTS. • 458

Administration of 0.1 mmol/kg of diquat to Fischer-344 rats causes acute hepatic necrosis by mechanisms that appear to involve increased generation of reactive oxygen species (ROS). The oxidation of biological molecules should be pivotal in the expression of the injury, but the specific targets critical to expression of this injury are not known. Hepatic DNA fragmentation (% of total) was increased in diquat-treated animals (6.7±0.3 vs. 24.9±5.1 at 2 h; 4.6±0.3 vs. 57.2±4.1 at 6 h, P<0.001) and oligonucleosomal fragmentation of hepatic DNA was observed. However, 8-OHdG contents in hepatic DNA were not increased by diquat (35.3±6.2 mol 8OHdG/106 mol dG) over controls (28.3±2.6). We assessed protein thiol status by derivatization of subcellular fractions with monobromobimane and separation of the fluorescent derivatives by SDS-PAGE. No differences from saline-treated controls were seen in animals 2 or 6 h after diquat, despite documentation of oxidant stress by contents of glutathione disulfide and of hepatic injury by elevation of plasma transaminase activities. Plasma ammonia concentrations increased in diquat-treated rats from 49±9 in controls to 170±22 μM 6 h after diquat(P<0.002). Hepatic glutamine synthetase activities were lower in diquat-treated rats (39.7±3.0 mU/mg pro) than in controls(65.8±3.4, P<0.001), but activities of carbamyl phosphate synthetase-I, which is a mitochondrial enzyme, were not decreased significantly. Supported by NIH grants GM44263 and GM39338.

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Smith, C., Gupta, S., Kleiner, H. et al. DNA FRAGMENTATION CAUSED BY REACTIVE OXYGEN SPECIES IN VIVO WITHOUT INCREASED 8-OH-dG CONTENTS. • 458. Pediatr Res 39, 79 (1996). https://doi.org/10.1203/00006450-199604001-00478

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