Dominique Singer

Respiratory response of malignant and placental cells to changes in oxygen concentration

Malignant cells and foetal tissues are exposed to low oxygen partial pressure (pO2) in situ due to the limited supply of oxygenated blood. Whether these cells have adapted to low pO2 or live under constant constraint is not clear. Herein, we compared the respiratory responses of different malignant cell types, maternal and foetal placental leucocytes, and benign cells by incubating them under a gradient of pO2, from saturation to hypoxia, in a high resolution respirometer. The malignant cells and foetal leucocytes showed higher rates of mitochondrial oxygen uptake compared to the benign cells and maternal leucocytes, respectively. On the other hand, the mitochondrial oxygen uptake rates of the hypoxia adapted cells declined faster than the other cell types during the onset of hypoxia, probably suggesting conformance of aerobic metabolism to the local oxygen concentration. The O2 consumption rate per million cells (JO2) of the malignant cells declined only when the O2 concentration ([O2]) decreased to values<or=10 microM. On the other hand, the JO2 of the benign cells declined with the decrease in [O2] from 200 to 40 microM and <or=10 microM. In the [O2] ranges outside these values the JO2 remained constant regardless of the decline of [O2] in the medium. The JO2 of foetal leucocytes and malignant cells responded to the change in [O2] in a similar manner, and may indicate comparable mechanisms of adaptation to hypoxia.