pH effects on the lifespan and transformation frequency of Syrian hamster embryo (SHE) cells

We have investigated the effects of modification of the growth media pH on Syrian hamster embryo (SHE) cellular lifespan and transformation. Culturing SHE cells in Dulbecco's modified Eagle's medium (DMEM) at pH 6.7 relative to pH 7.3 results in a 4-fold increase in the lifespan of SHE cells before senescence occurs. This effect was observed both with the wild type SHE cell population and with the morphological transformation sensitive subpopulations derived from the wild type SHE cell mixture (cl9 and cl17). The increase in SHE cell lifespan at pH 6.7 was observed both as an increase in days in culture and an increase in the number of total population doublings before cellular senescence occurred. The tumor promoting agent TPA increased the lifespan of the SHE cell population and one of the MT sensitive subpopulations when these cells were cultured in pH 7.3 medium. Interestingly, treatment of the SHE cell population, and the two MT sensitive SHE cell clones with TPA at culture medium pH of 6.7 reduced the lifespan of each cell type. Finally, culturing SHE cells in medium of pH 6.7 increased the potential of the cells to undergo morphological transformation in response to treatment with carcinogens, demonstrating a potential connection between SHE cell lifespan and carcinogen induced morphological transformation, probably through a mechanism involving a pH induced block in cellular differentiation. We believe this is the first report demonstrating the role of pH in controlling cellular lifespan.