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Effect of a Subcutaneously Growing Walker 256 Carcinosarcoma on Host Tissue Mitochondrial Function and Magnesium Content¹

Department of Clinical Oncology, University of Glasgow, 1 Horselethill Road, Glasgow G12 9LY, United Kingdom

Mitochondria were prepared from the liver, kidneys, and skeletal muscle of rats at 1, 6, 12, 18, and 26 days after inoculation with Walker 256 cells or sterile 0.9% NaCl solution and assessed for structural and functional integrity. Using polarography to measure respiration, it was found that all tissue mitochondria from both controls and tumor-bearing animals prepared 1 day after inoculations were damaged and had impaired respiratory function. This effect was believed to be caused by the presence of anesthetic molecules in the mitochondrial membranes rather than by tumor. On Day 6, all tissue mitochondria were respiring properly; no evidence of membrane disruption was apparent. From Day 12 onwards, mitochondria from the tumor-bearing animals would not consume oxygen unless magnesium ions were added to incubation media. Kidney required by far the greatest amount of magnesium, in one case, 10 mM MgCl₂. The requirement of the liver never exceeded 3 mM MgCl₂, and with the muscle no dependency developed. The quantity of magnesium ions necessary to restore normal kidney mitochondrial function increased with tumor size (r = 0.83). From Day 12 onwards, mitochondria prepared from the control animals respired normally, and all mitochondria from the controls and the tumor-bearing rats were structurally intact.

When the magnesium content of the abnormal mitochondria prepared from the animals inoculated with tumor cells was measured by atomic absorption spectrophotometry, the mitochondria were found to be deficient by 18% for kidney (p < 0.01) and 20% for liver (p < 0.01) compared to controls (Student's t test).

¹ This work was supported with a grant (CRC SP1429 P01) from the Cancer Research Campaign, London, England. Part of this work has already appeared in abstract form (7).

² To whom requests for reprints should be addressed.

Received 9/22/83. Accepted 12/14/83.