Adenine nucleotide transport in hepatoma mitochondria and its correlation with hepatoma growth rates and tumor size

Randall L. Barbour, Samuel H.P. Chan

Research output: Contribution to journalArticle

13 Scopus citations

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. Results obtained demonstrate that (a) the apparent K™ and Vmax values for adenosine diphosphate and adenosine triphosphate uptake are significantly lower in hepatoma compared to normal or regenerating liver mitochondria, (b) the Vmax values for adenosine diphosphate uptake correlate with tumor growth rate, and (c) the K™ values for adenosine triphosphate 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. Studies examining the causes of reduced transport rates in hepatoma mitochondria showed that they are independent of the mitochondrial energy state and associated with substantially lower levels of the total and exchangeable adenine nucleotides. Additional studies revealed that 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 to 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.

Original languageEnglish (US)
Pages (from-to)1511-1517
Number of pages7
JournalCancer Research
Volume43
Issue number4
StatePublished - Apr 1 1983

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Adenine nucleotide transport in hepatoma mitochondria and its correlation with hepatoma growth rates and tumor size'. Together they form a unique fingerprint.

  • Cite this