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Citrate Accumulation in Slices of Transplantable Tumors of the Rat^*

( Department of Pharmacology, University of Illinois, College of Medicine, Chicago 12, Ill.)

1. In the presence of a variety of substrates of the citric acid cycle, sodium fluoroacetate, and an atmosphere of 100 per cent oxygen, slices of transplantable rat tumors accumulated 4.5–6.1 µmoles of citrate/gm/2 hr. Under similar conditions, slices of liver, brain, diaphragm, and spleen accumulated 6.3–7.7 µmoles of citrate/gm/2 hr, while kidney slices accumulated 26–38 µmoles of citrate/gm/2 hr.

2. Maximal citrate was produced by kidney slices in the presence of pyruvate and succinate, by liver slices in the presence of pyruvate, fumarate, and oxalacetate, by spleen and brain in the presence of glutamate, pyruvate, fumarate, and oxalacetate, and by Walker and Jensen tumors and diaphragm in the presence of glucose, glutamate, pyruvate, fumarate, and oxalacetate.

3. Maximal citrate in tumor and liver slices was also produced in the presence of bicarbonate, pyruvate, and glucose. A decrease in the pH of the medium from 7.4–5.5 depressed citrate formation of liver slices by 75–80 per cent, while lactate production was reduced by only 36 per cent.

4. In systems containing liver, kidney, and tumor slices, citrate formation was increased with increasing atmospheric oxygen tension.

5. These studies indicate that tumors have the capacity to form citrate in vitro in the presence of excess substrate and high atmospheric oxygen tension. The lack of activity of tumors in the formation of citrate in fluoroacetate-treated animals would appear to be a consequence of low oxygen tension, associated with a lack of essential substrates and reduced intratumor pH.

6. These studies re-emphasize the necessity of differentiating between in vitro studies on tumors which can provide a measure of maximal metabolic capacities and in vivo studies which provide a measure of activity of tumors in their natural environment.

^* Supported by grants from the American Cancer Society, the Jane Coffin Childs Fund, and the Josephine Arnold Fund.

Received 4/22/57.