Subcellular localization of 57Co-bleomycin in normal and tumor tissues.

57Co-bleomycin appears to be one of the best tumor detecting agents at the moment. The localization within the cells is not yet known. This preclinical investigation had the aim to study the subcellular distribution of 57Co-bleomycin in liver, spleen and tumors of rats and mice. Mice with transplanted lymphosarcoma and osteosarcoma were used and rats with transplanted rhabdomyosarcoma. The concentration of 57Co-bleomycin was 2 to 10 times higher in the tumors as compared to the (normal) liver. This accumulation property was not found with the control substance: 57CoCl2. The highest radioactivity of 57Co-bleomycin (cpm/mg protein) was observed in subcellular fractions containing mitocohndria and lysosomes. After treatment of these fractions with hypertonic solutions it could be shown that enzymes of the mitochondrial matrix remained inside the vesicles under conditions of almost complete release of 57Co-bleomycin. Half of the lysosomal enzyme acid phosphatase was released too. From these experiments it is concluded that 57Co-bleomycin is preferentially localized in heavy secondary lysomes which are more fragile than the lighter lysosomes in the cells.