STUDIES ON THE MECHANISM OF ANTITUMOR EFFECT OF BLEOMYCIN ON SQUAMOUS CELL CARCINOMA

Distribution of 3H-bleomycin among organs of normal mice of various ages and old mice bearing skin carcinoma or sarcoma induced by 20-methylcholanthrene was studied and the ratios of the antibacterial activity to the radioactivity were examined. Higher concentration was shown in carcinoma than in sarcoma and in the former more than 50% of 3H-bleomycin remained in an active form exhibiting antibacterial activity. Slight or no activity was observed in sarcoma. The selective effect of bleomycin on mouse skin carcinoma induced by 20-methylcholanthrene was thus suggested to be due to the low ability of the tumor to inactivate bleomycin and probably also to the high uptake in this tumor. Differences were also observed among distributions of 3H-bleomycin in lung and skin of mice of different ages. The higher concentration of its active form was shown in lung and skin of old mice at higher rate than in those of young ones. An enzyme that releases one mole of ammonia from bleomycin and which inactivates bleomycin was extracted from tissues. The bleomycin inactivating activity of the enzyme protein was significantly lower in the protein extracted from squamous cell carcinoma of mice skin induced by 20-methylcholanthrene than in that extracted from sarcoma induced by the same chemical.