ADENINE-NUCLEOTIDE TRANSPORT IN HEPATOMA MITOCHONDRIA AND ITS CORRELATION WITH HEPATOMA GROWTH-RATES AND TUMOR SIZE

  • 1 January 1983
    • journal article
    • research article
    • Vol. 43  (4) , 1511-1517
Abstract
Initial rates of [3H]adenosine diphosphate and [3H]adenosine triphosphate uptake were measured in mitochondria isolated from normal rat liver, regenerating liver, mouse hepatoma BW7756, and four Morris hepatomas (7777, 7800, 7794A and 16) of varying degrees of malignancy. The apparent Km and Vmax values for ADP and ATP uptake are significantly lower in hepatoma compared to normal or regenerating liver mitochondria. The Vmax values for ADP uptake correlate with tumor growth rate. The Km values for ATP in both hepatoma and normal mitochondria are lowered in the presence of added uncoupling agents; however, the extent of decrease is much less in fast-growing tumors than in slow-growing tumors and normal tissues. The reduced transport rates in hepatoma mitochondria are independent of the mitochondrial energy state, and associated with substantially lower levels of the total and exchangeable adenine nucleotides. Transport rates are also dependent on the size of the tumor from which the mitochondria are isolated. Mitochondria isolated from small tumors (< 2 g) had higher transport rates as well as higher levels of exchangeable and total adenine nucleotides than those isolated from larger tumors (4-6 g). Endogenous inhibitor levels also varied as a function of tumor size; free fatty acid levels increased, whereas acyl coenzyme A levels declined in mitochondria isolated from larger tumors. These results seem to indicate that, during the progression of tumor growth, mitochondria are experiencing cellular environmental changes that will affect overall tumor cell metabolism.