Ultrastructural changes induced by a-sarcin in a human pulmonary tumor grown in naked mice

Abstract

a-Sarcin is a cytotoxic polypeptide produced by Aspergillus giganteus. It suppresses protein synthesis in yeast and wheat germ extracts and has a purine-specific RNase activity. The substance has been tested for its antitumor properties in a series of induced tumor systems in mice such as sarcoma and carcinoma among others. Although some of the in vitro effects of a-Sarcin on certain cellular components have been elucidated, the biological effects leading to cellular damage are still obscure. In this work we analysed the morphological changes in tumor cells derived from human pulmonary adenocarcinoma heterotransplanted and grown in naked mice, induced shortly (24 hours) after a single intratumoral injection of U-Sarcin (0.4 mgltumor). The results obtained were: 1) swelling of mitochondria; 2) cell necrosis with partial removal of necrotic cells by phagocytosis; 3) thickening of interlobular connective tissue; 4) hyperplasia of globet-cell-like clear cells. The mode of action concerning these cellular changes is presently uncertain. In view of the severity of these structural alterations it seems conceivable that a-Sarcin may enter the cell undergoing interactions with different intracellular structures. This would require a selective membrane permeabilization, perhaps induced upon formation of complexes with negatively-charged membrane phospholipids