Hydrogen peroxide$({\rm H}_{2}{\rm O}_{2})\text{-resistant}$ variants of the Chinese hamster ovary HA-1 line have been derived by culturing cells in progressively higher concentrations of H2 O2 (>200 days, in 50-800 μM H2 O2). The${\rm H}_{2}{\rm O}_{2}\text{-resistant}$ phenotype has been stable for over 60 passages (240 days) following removal from the H2 O2 stress. The resistant cells demonstrate both increased capacity to deplete exogenously added H2 O2 from the growth medium and increased catalase activity. H2 O2 resistance correlates well with catalase activity. An increase in chromosome number occurred in the cells adapted to 200-800 μM H2 O2, but increases in aneuploidy and tetraploidy were not necessary for resistance. These results suggest that adaptation to chronic oxidative stress mediated by H2 O2 in mammalian cells is accompanied by a stable heritable change in expression of catalase activity.

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