Mammalian resistance to oxidative stress: a comparative analysis

Changes in gene expression represent a major protective mechanism, and enforced overexpression of individual genes has been shown to protect cells. However, no large-scale comparison of genes involved in mammalian oxidative stress protection has yet been described. Using filter microarray and restriction fragment differential display technology, hydrogen peroxide (H2O2)-resistant variants of hamster HA-1 fibroblasts and human HL-60 promyelocytes were found to possess a surprising lack of commonality in specific modulated genes with the single exception of catalase, supporting the hypothesis that catalase overexpression is critical for resistance to H2O2. Comparison of two cell lines from the same species (hamster) selected with an exogenous oxidative stressing agent (H2O2) and an endogenous metabolic oxidative stressing agent (95% O2) also revealed little commonality in modulation of specific mRNAs with the exception of glutathione S-transferase enzymes and catalase. Acute oxidative stress in HL-60 led to the modulation of a limited subset of the genes associated with chronic oxidative stress resistance. Overall, these results suggest that mammalian resistance to oxidative and perhaps other stress does not require a significant number of common genes but rather only a limited number of key genes (e.g., catalase in our model systems) in combination with others that are cell type and stress agent specific.