Haemorrhagic tumour necrosis following endotoxin administration. I. Communication: morphological investigation on endotoxin-induced necrosis of the methylcholanthrene (Meth A) tumour in the mouse.

Endotoxin induced necrosis of the Meth A mouse tumour has been investigated using macroscopic, histological and ultrastructural examination methods. On the 8th day after tumour cell transplantation, the animals received a relatively non-toxic dose of the Salmonella abortus equi endotoxin intravenously. The natural history of the tumour necrosis took the following course: The earliest morphological changes could be seen with the electron microscope 90 min after administration of the endotoxin, and were seen as an interstitial oedema with separation of the tumour cells. Haemorrhagic necrosis of the tumour was complete 4 hours after injection, and could be easily recognized with the naked eye. Rejection of the necrotic malignant tumour was complete two weeks after LPS administration. Only minor residual scarring of the belly-wall remained. Haemorrhagic tumour necrosis due to endotoxin can be compared with the localized Shwartzman reaction and probably involves tumour necrotizing factor (TNF). For complete destruction of a tumour by haemorrhagic necrosis the size of the tumour is critical. Certain regression after endotoxin administration depends upon additional T-cell-mediated immunity (provided the tumour is immunogenic). In contrast to the haemorrhagic necrosis, BCG-induced tumour regression is accompanied by granulomatous inflammation, which may be responsible for destruction of the tumour.