Maintenance of genomic integrity in mammalian kidney cells exposed to hyperosmotic stress

Changes in environmental salinity/osmolality impose an osmotic stress upon cells because, if left uncompensated, such changes will alter the conserved intracellular ionic milieu and macromolecular density, for which cell metabolism in most extant cells has been optimized. Cell responses to osmotic stress include rapid posttranslational and slower transcriptional events for the compensatory regulation of cell volume, intracellular electrolyte concentrations, and protein stability/activity. Changes in external osmolality are perceived by osmosensors that control the activation of signal transduction pathways giving rise to the above responses. We have recently shown that the targets of such pathways include cell cycle-regulatory and DNA damage-inducible genes (reviewed in Kültz, D., 2000. Environmental stressors and gene responses, Elsevier, Amsterdam. pp 157-179). Moreover, recent evidence suggests that hyperosmotic stress causes chromosomal aberrations and DNA double-strand breaks in mammalian cells. We propose that the modulation of cell cycle checkpoints and the preservation of genomic integrity are important aspects of cellular osmoprotection and as essential for cellular osmotic stress resistance as the capacity for cell volume regulation and maintaining inorganic ion homeostasis and protein stability/activity.