The effect of oxygen tension on the growth and metabolism of a mammalian cell

Abstract

1. 1. The studies reported here were performed with a mammalian cell, designated AH, which is similar in morphological and biochemical properties to the strain L mouse fibroblast. It is cultivated serially in free suspension. 2. 2. Multiplication of AH cells may be obtained in absolute nitrogen, i.e., in the virtual absence of oxygen. However, the rate is lower in moderate oxygen levels, and there is a marked sensitivity to experimental manipulation. 3. 3. Optimum growth is obtained from 10–35 per cent oxygen. In high oxygen tensions, cell proliferation is strongly inhibited. The inhibition may be reversed by lowering the oxygen tension within 48 hr. After longer periods of incubation in high oxygen, irreversible changes, including cellular degeneration, occur. 4. 4. The oxygen inhibition is apparently not mediated by hydrogen peroxide, since no accumulation of the latter could be detected. Added catalase or reducing agents also did not alleviate the inhibition. 5. 5. High concentrations of catalase (10 −6−10 −7 M) cause cessation of growth and rapid cellular degeneration. Added hydrogen peroxide and/or ethanol did not markedly alter this inhibition. 6. 6. No effects of high oxygen tension on glucose uptake, lactate production, and uptake of radioactive phosphate into cellular constituents was noted in short-term experiments. In long-term experiments the uptake of radioactive phosphate into nucleic acids, especially DNA, was markedly lower in 95 per cent oxygen than in 20 per cent oxygen. 7. 7. Cultivation of AH cells in absolute nitrogen, 20 or 95 per cent oxygen, did not result in marked alteration in the total soluble acid-labile phosphate compounds, nor in the quantities or proportions of adenine nucleotide present ultracellularly. 8. 8. The metabolic data are consistent with a rather specific inhibition by high oxygen tension at a site or sites closely linked with the process of cell multiplication.