Mechanisms of enhanced intrahepatic metastasis in surfactant‐treated hamsters; An electron microscopy study

A metastasizing lymphoma (ML) in hamsters, grafted into the subcutaneous tissues, gives rise to moderate numbers of nodular intrahepatic deposits; but if the animals are treated with the surfactant triton‐WR 1339 (four intraperitoneal injections, 1,000 mg/kg body weight) the liver is massively and diffusely involved with secondary tumour. The results of serial ultra‐structural studies now indicate some explanations for this finding. The major factor appears to be that triton‐WR inflicts mechanical damage on cells of the sinusoidal lining, primarily as a result of lysosomal lesions which distend and distort the cells; this substantially facilitates the egress of tumour cells from the circulation into the extrahepatic tissue. Two possible subsidiary mechanisms are also considered: (1) Extensive lysosomal damage seen in Küpffer cells and in free, intravascular macrophages may perhaps result in impaired phagocytic activity within the liver; (2) Drug‐induced lysosomal damage in hepatic parenchymal cells may favour the establishment of tumour cells lying in the extravascular space. Triton‐WR is reported to exert an antifibrinolytic effect but this is apparently irrelevant to the enhanced intrahepatic growth of ML; there is no evidence that fibrin plays any part in the metastatic spread of this tumour.