ENDOGENOUSLY GENERATED ACTIVE OXYGEN SPECIES AND CELLULAR GLUTATHIONE LEVELS IN RELATION TO BHK-21 CELL-PROLIFERATION

In BHK-21 cells (baby hamster kidney fibroblasts) cellularly generated active oxygen species such as hydrogen peroxide and superoxide appear to be important growth regulatory signals as judged from the growth inhibitory effects of catalase, superoxide dismutase and superoxide dismutase mimics. These active oxygen species may contribute a novel redox system of regulatory control superimposed upon established growth signal pathways. This may be achieved by direct oxidative modification of cell regulatory proteins such as transcription factors or protein kinases or indirectly through, for example alterations in levels of glutathione (GSH). This latter possibility is suggested from observations that catalase, or superoxide dismutase treatment of BHK-21 cells brings about increased cellular levels of GSH. However during the normal growth phase cellular levels of GSH actually decline although this effect can be partly reversed by N-acetylcysteine and by mercaptosuccinate which also impair proliferation of these cells.