HYDROGEN-PEROXIDE AND THE PROLIFERATION OF BHK-21-CELLS

Intracellular levels of H2O2 in BHK-21 cells are not static but declin e progressively with cell growth. Exposure of cells to inhibitors of c atalase, or glutathione peroxidase, not only diminishes this decline b ut also depresses rates of cell proliferation, suggesting important gr owth regulatory roles for those antioxidant enzymes. Other agents whic h also diminish the growth-associated decline in intracellular levels of H2O2, such as the superoxide dismutase mimic, copper II - (3,5-diis opropylsalicylate)(2), or docosahexaenoic acid, also reduced cell prol iferation. In contrast, proliferation can be stimulated by the additio n of 1 mu M exogenous H2O2 to the culture medium. Under these conditio ns, however, intracellular levels of H2O2 are unaffected, whereas ther e is a reduction in intracellular levels of glutathione. It is argued that critical balances between intracellular levels of both H2O2 and g lutathione are of significance in relation both to growth stimulation and inhibition. In addition growth stimulatory concentrations of H2O2, whilst initially leading to increased intracellular levels of lipid p eroxidation breakdown products, appear to ''trigger'' their metabolism , possibly through aldehyde dehydrogenase, whose activity is also stim ulated by H2O2.