SUPPRESSION OF APOPTOSIS BY OVEREXPRESSION OF BCL-2 OR BCL-X(L) PROMOTES SURVIVAL AND MUTAGENESIS AFTER OXIDATIVE DAMAGE

Apoptosis is the physiological process by which unwanted cells in an o rganism are killed. Bcl-2, a membrane-bound cytoplasmic protein, and i ts close relative Bcl-X-L, are both effective inhibitors of apoptosis induced by a wide variety of stimuli in many different cell types. In a previous study, we reported that suppression of apoptosis by BCl-2 o r Bcl-X-L, markedly elevates the levels of radiation-induced mutations at the specific locus thymidine kinase. We investigated the effect of the Bcl-2 or Bcl-X-L overproduction on hydrogen peroxide-induced muta genesis. Oxidative DNA damage has been implicated in biological proces ses such as mutagenesis, carcinogenesis and aging. Overexpression of e ither Bcl-2 or Bcl-X-L enhances oxidative stress mutagenesis in cells with wild type p53 as well as with mutated p53 protein. These results support the hypothesis that apoptosis plays a crucial role in maintain ing genomic integrity by selectively eliminating highly mutated cells from the population.