| Summary: | Hypoxia and acidosis are hallmarks of tumors as well as critical determinants of response to treatments. In present study, we investigate the extent to which changes in O2/CO2 gas ratio may affect the pH and subsequently initiate cell death in malignant neuroblastoma. The data indicate that cell death occurred in either a closed chamber containing 100% oxygen or atmosphere (.05%CO2) after 24hrs of exposure at 37°C. These effects were also accompanied by a rise in pH within cell culture medium. Under both conditions, toxicity was potentiated by the addition of sodium bicarbonate but prevented by neutralization with acetic acid. In contrast, cells grown in a closed chamber containing 100% pure CO2 underwent cell death tantamount to a drop in pH resulted from the build up of carbonic acid. Under these conditions, toxicity was exacerbated by acetic acid and reversed by neutralization with sodium bicarbonate. These data clearly indicate that while O2 appears to be toxic to cancer cells, the rise in alkalinity is the determining factor in cell death. Moreover, the pH range to which cells thrived was 5.6 to 7.4, where a slight rise in basic pH from 7.4 to 8.0, corresponded to dose dependent cell death mediated by higher levels of O2. These findings suggest a paramount role for alkalinity rather than O2 itself in mediating adverse effects on tumor cells. (Supported by NIH grant NCRR: RR 03020)
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