Mitotically active, growth-arrested cells and proliferatively senescent cultures of human fetal lung fibroblasts (WI-38) were exposed to six different oxygen tensions for various lengths of time and then analyzed to determine the responses of their antioxidant defense system. Glutathione (GSH) concentration increased as a function of ambient oxygen tension in early passage cultures; the effect was larger in exponentially growing cultures than in those in a state of contact-inhibited growth arrest, but was absent in senescent cells. Conversely, the activity of glutathione disulfide reductase was greater in growth-arrested cultures than in mitotically active cells irrespective of oxygen tension. Glucose-6-phosphate dehydrogenase was lowest in log-phase cells exposed to different oxygen tensions for 24 h and in senescent cells. Both hypoxia and hyperoxia depressed selenium-dependent glutathione peroxidase activity in early passage cultures, while the activity of the enzyme progressively declined with increasing oxygen in senescent cells. The GSH S-transferase activity was unresponsive to changes in ambient oxygen tension in either young or senescent cultures. Manganese-containing superoxide dismutase (MnSOD) activity was unaffected by oxygen tension, but was elevated in young confluent cultures as compared with cultures in log-phase growth. MnSOD activity was significantly higher in senescent cultures than in early passage cultures and was also responsive to increased oxygen tension in senescent cultures. Copper–zinc-containing superoxide dismutases activity was not affected by oxygen tension or the passage of time, but it declined in senescent cultures.

Free radicals and other reactive oxygen species are produced in the metabolic pathways of aerobic cells and affect a number of biological processes. Oxidation reactions have been postulated to play a role in aging, a number of degenerative diseases, differentiation and development as well as serving as subcellular messengers in gene regulatory and signal transduction pathways. The discovery of the activity of superoxide dismutase is a seminal work in free radical biology, because it established that free radicals were generated by cells and because it made removal of a specific free radical substance possible for the first time, which greatly accelerated research in this area. In this review, the role of reactive oxygen in aging, amyotrophic lateral sclerosis (a neurodegenerative disease), development, differentiation, and signal transduction are discussed. Emphasis is also given to the role of superoxide dismutases in these phenomena.