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Novartis Found Symp. 2001;240:46-62; discussion 62-7, 152-3.

Why are cancers acidic? A carrier-mediated diffusion model for H+ transport in the interstitial fluid.

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  • 1CRC Biomedical Magnetic Resonance Research Group, Department of Biochemistry and Immunology, St George's Hospital Medical School, London, UK.


31P MRS studies have shown that the intracellular compartment ot tumours is kept near neutrality, whereas the interstitial fluid is acidic (pH 6.5-6.8). Why is this compartment acidic? Balance studies confirm that tumours produce excessive lactic acid, although less than usually supposed, but this cannot be the whole story, since Tannock and co-workers have shown interstitial acidity in glycolysis-deficient tumours. Another major acid load is caused by hydration of CO2 molecules to carbonic acid, catalysed by carbonic anhydrase. The distance that H+ must diffuse from cancer cells to capillaries is further than in normal tissue and this will increase acidification near the cells. We show that previous quantitative models based on simple H+ diffusion are unsatisfactory. This is because most H+ ions cross the interstitial space bound to buffers such as inorganic phosphate. Although these protonated buffers (i.e. conjugate acids) diffuse much more slowly than H+ ions they carry most of the protons, so the pH predicted by this model is closer to neutrality for a given proton production rate than that predicted by the dissolved H+ model. We have developed a mathematical model of this carrier-mediated system that predicts pHe values as low as those observed in some tumours.

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