Calcium uptake in vitro by beef heart mitochondria under the influence of Adriamycin

Abstract

Adriamycin, an antibiotic which has proven to be a clinically useful chemotherapeutic agent against cancer, is found to produce fatal, dos~-related cardiac toxicity in man. Although the mechanism of this adriamycin-induced cardiomyopathy remains elusive, structural studies of affected patients and laboratory animals indicate that Adriamycin causes delayed structural alterations in the form of myocardial lesions. Recent studies have demonstrated elevated levels of calcium in tissue affected by Adriamycin, and microscopic examination of the degenerating heart tissue reveals mitochondrial degeneration and dense body formation within mitochondria in the form of calcium phosphate deposits. Therefore, it was decided to investigate the effect of Adriamycin upon calcium uptake in vitro by beef heart mitochondria, and to see how the combination of Adriamycin and A-23187 (which has a known effect upon calcium flux) affect mitochondrial calcium movement. Results obtained in this paper indicate that Adriamycin induces accumulation of calcium by heart mitochondria. Crucial to this study was the technique of atomic absorption spectroscopy used to determine calcium concentration which is based upon the absorption of energy by valence electrons of ground state calcium atoms. Use of a nitrous oxide-acetylene flame (hot) as opposed to an air-acetylene flame (cooler), based on the interference relevant in each case) is briefly discussed.