SUPEROXIDE IS NOT THE PROXIMATE CAUSE OF PARAQUAT TOXICITY

Paraquat toxicity is thought to occur through the production of supero xide (O-2(.-)) and it has been argued that this oxygen radical species is, itself, an important mediator of the toxicity of this drug. If so , a direct relationship should exist between the steady-state amounts of O-2(.-) produced and the lethal effects of paraquat. We have theref ore examined O-2(.-) mediated chemiluminescence and paraquat sensitivi ty in bacteria with widely varying superoxide dismutase (SOD) activiti es. As expected, bacteria with high SOD activity exhibit minimal (luci genin enhanced) chemiluminescence in the presence of paraquat whereas SOD-deficient bacteria show >90-fold higher chemiluminescence compared to parental strains. Nonetheless, high SOD bacteria are more readily killed by paraquat whereas SOD-deficient organisms show no increased s usceptibility to this agent. This further supports our earlier conclus ions that hypertrophied SOD activity is inadequate defense against par aquat and that O-2(.-) is probably not the proximate toxin by which pa raquat mediates cellular injury.