Early mitochondrial damage in the induction of haemorrhagic necrosis in the Crocker sarcoma (S 180) by endotoxin.

Disturbances in the functional properties of tumor mitochondria have been studied during the course of induction of haemorrhage brought about by endotoxin in the murine Crocker sarcoma (S 180). Extensive impairment of function was already present in mitochondria isolated from control tumors, as shown by low respiratory control ratios. The existing mitochondrial damage intensified promptly in response to injection of endotoxin long before the onset of haemorrhage at 4 h. The nature of the additional damage took two forms, depending on the duration of exposure to endotoxin; first, at 30 min, a true uncoupling of oxidative phosphorylation was seen, largely reversible in vitro by pre-treatment of the isolated organelles with bovine serum albumin (BSA). Second, at 1 h and later, oxygen utilisation in the presence of succinate, ADP and inorganic phosphate (Pi) was depressed. The pre-addition of BSA consistently lowered respiration rates with succinate and Pi in all preparations. The extent of endogenous inhibition of the adenine nucleotide translocase appeared unaltered by endotoxin in vivo.