alpha-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
alpha-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
alpha-Sarcin (0.4 mg/
tumor). 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 goblet-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
alpha-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.