Relevance of oxidative stress to the limited replicative capacity of cultured human diploid cells: the limit of cumulative population doublings increases under low concentrations of oxygen and decreases in response to aminotriazole.

Human diploid cells, TIG-7, were serially cultivated under 1%, 5% or 21% (air) oxygen. The limit of their cumulative population doublings was extended by 16% or 10% under 1% or 5% oxygen, respectively, as compared with that under 21% oxygen. When TIG-7 cells were serially cultivated in the presence of 10 mM or 20 mM 3-amino-1H-1,2,4-triazole, an inhibitor of catalase scavenging hydrogen peroxide, the limit of their cumulative population doublings was shortened by 4.4% or 14.4%, respectively, as compared with untreated cells. In addition, long-term, rather than short-term, exposure of TIG-7 cells to aminotriazole retarded cell growth. Treatment with aminotriazole caused decreases not only in catalase activity but also in superoxide dismutase activity and reduced glutathione concentration, and an increase in glutathione peroxidase activity. These results suggest that the limit of the cumulative population doublings of human diploid cells is extended or shortened under decreasing or increasing oxidative stress, respectively. Oxidative stress may be relevant to replicative capacity, and a causative factor for oxidative stress may be hydrogen peroxide.