PHYSIOLOGICAL OXYGEN-TENSION IS RELEVANT TO MHC-1 EXPRESSION, SPONTANEOUS TRANSFORMATION, AND INTERFERON RESPONSE OF IN-VITRO AGING MURINE FIBROBLASTS

Working from the hypothesis that modest deviations from physiological oxygen tension will influence cell characteristics important for infec tions/immunity and tumor development, cells were studied at three oxyg en tensions during in vitro aging. Primary mouse embryo fibroblasts we re established and subsequently passaged at 3, 6, and 18 kPa oxygen te nsion (6 representing normal tissue tension and 18 being the conventio nally tension at in vitro cultures). The growth rate was slightly high er at 6 than 3 and 18 kPa. All cultures eventually stopped growing and subsequently transformed to nonmalignant cells with unlimited growth capacity. Cells kept at 3 kPa reached the highest number of cell doubl ings before crisis. Stimulation with PolyI:C resulted in detectable in terferon response only at the high oxygen tension, and after transform ation none of the cultures responded with interferon production. Expre ssion of the major histocompatibility complex H-2K was elevated above and below physiological oxygen tension, indicating regulatory processe s optimizing MHC expression at about physiological oxygen tension.