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 mitochondria 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 lysosomes which are more fragile than the lighter lysosomes in the cells.