Peroxide resistance in human and mouse lens epithelial cell lines is related to long-term changes in cell biology and architecture

It is well established that the response of the cell to environmental stress is a major basis for cell modification. Such modification is believed to adapt the cell to better survive its environment. Oxidative stress, a major and ubiquitous stressing factor, was selected for investigating the cellular response to stress. Most studies investigating such cellular response have employed examination of the cell either during or shortly after exposure to stress. We have employed a different approach arguing that the short-term response to stress obscures the biological changes that allow the cell to continue to thrive in its new environment. Reflecting this concept, murine and human cell lines capable of surviving regular exposure to toxic levels of H ₂O₂ or TBOOH have been developed. It was found that certain fundamental long-term changes in cell biology had occurred. The peroxide-resistant cells are diploid rather than aneuploid, show fundamental changes in the cytoskeletal cellular structure, suggesting less rigid more flexible cells, express a new lower molecular mass of p53, a key stress protein responder involved in adaptation, and finally have an immunochemical modification in αA-crystallin, a small heat-shock protein. Previously, it was found that there is a dramatic increase in catalase and gluthathione S-transferase activity and a remarkable limited change in expression in other antioxidative genes in these cells. The impact of these changes is discussed. It is apparent that evolutionary cell modifications can occur in response to relatively rapid changes in environment over periods ranging from days to months rather than the thousands of years considered in most evolutionary modifications.