EFFECTS OF OXYGEN-PRESSURE AND MEDIUM VOLUME ON THE TOXICITY OF PARAQUAT IN RAT AND HUMAN TYPE-II PNEUMOCYTES

The herbicide, paraquat is highly toxic for mammals, with the lungs be ing the main target organ, because of the active accumulation of the c ompound in this organ, The cellular toxicity of paraquat has been show n to be an O-2-driven process and hyperoxia is known to increase the l ethality of paraquat, In this study we have examined the effect of var ious O-2 concentrations on the toxicity of paraquat in rat and human t ype II pneumocytes in culture, and we have tested whether the thicknes s of the liquid layer above the cells would influence the toxicity of paraquat, Type II pneumocytes were isolated from rat or human lung tis sue using trypsin digestion, Percoll density gradient centrifugation a nd differential attachment. Adherent cells (day 2) were incubated for 20 h in different volumes of culture medium (thickness of liquid layer ), whether or not in the presence of paraquat, in the presence of diff erent O-2 tensions. The viability of the cells was assessed by the rel ease of LDH in the culture medium, In both rat and human type II pneum ocytes the toxicity of paraquat was independent of the thickness of th e liquid layer (2.5 to 10 mm height), The toxicity of paraquat in rat type II pneumocytes decreased from a TC50 value of 28 mu M paraquat at 21% O-2 to 107 mu M at 10% O-2 and increased to 12 mu M and 8 mu M at 60% and 85% O-2, respectively. For human type II pneumocytes the TC,, values were 7 mu M; 25 mu M and > 1000 mu M paraquat at 60%, 21% and 10% O-2, respectively, In this study we have shown that the diffusion of O-2 through a liquid layer does not limit the toxicity of paraquat and that, as in vivo, increasing O-2 partial pressure enhances the tox icity of paraquat.