DRUG-INDUCED INTERFERENCE WITH ENERGY-METABOLISM IN THE S180 SARCOMA - A NEW PRINCIPLE IN THE PRODUCTION OF SELECTIVE TUMOR INJURY

  • 1 January 1981
    • journal article
    • research article
    • Vol. 2  (3) , 155-164
Abstract
The effects of low doses of L-isoproterenol and hydralazine on energy production in the [mouse] S180 sarcoma were examined in vivo. Both substances produced dramatic alterations in the tumor adenine nucleotide pattern (TANP) in 1 h, the tumor ATP level falling by 80-84% and the energy charge dropping from 0.81 to 0.27-0.28. The approximate ratios of highest amount tolerated by the animal to lowest effective anti-tumor dose were 500 and 15, respectively. The highest tolerated doses of the drugs produced minor and quite dissimilar effects on the adenine nucleotide pattern of mouse liver in 1 h. At 24 h after the initial drug treatment the TANP had largely returned to normal but total losses of adenine nucleotides of 38-69% were recorded. The effect of hydralazine was more marked and more reproducible than that of L-isoproterenol. Initial treatments with either drug established a refractory state in the tumor by 23-24 h; 2nd administrations 1 h before death had only modest effects on the TANP. Despite alterations in the macroscopic appearance of the injured tissue, necrosis was not histologically evident 24 h after treatment but extensive necrotic areas were readily visible at 5 days.