Glutathione in the cellular defense of human lung cells exposed to hyperoxia and high pressure

Saturation diving involves exposure to elevated partial pressure of oxygen (Po-2) and high pressure. The present work demonstrated that hyperoxic expo sure for up to 72 h had significant effects on human lung fibroblasts. Fort y to sixty kPa Po-2 had severe acute toxic effects, and 60 kPa O-2 reduced plating efficiency approximately 96% and completely inhibited cell prolifer ation. Long-term toxic effects were observed as a persistent reduction of c ell growth rate after 24 h exposure to 60 kPa O-2 in helium, suggesting gen etic effects or induction of cellular senescence. No effect of high pressur e per se was observed in this respect Cellular glutathione was increased up to a plateau 40-50% above control level after an initial decrease, which m ay indicate toxic effects during the GSH depletion period. The glutathione egress increased even more than the intracellular level after exposure to t hese conditions. The effects on glutathione were growth state specific with the highest response in exponentially growing cells. Slight protective eff ects of high pressure were noted in a cell growth assay, correlating with a reduced response on the glutathione level. The results support previous st udies indicating that hyperoxia is the main contributor to the adverse effe cts of exposure to high Po, and high pressure and point to the involvement of glutathione in the cellular detoxification of reactive oxygen species un der these conditions.