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 enzymethat releases one mole of ammoniafrom bleomycin and which inactivates bleomycin was extracted from tissues. The bleomycin inactivating activity of the enzymeprotein 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.
The antitumor effect, distribution among various organs and toxicity of formycin and formycin B are studied. Formycin inhibits of Ehrlich carcinoma and L-1210, with stronger activity on the solid form than on the ascites form. Formycin B shows no inhibition of Ehrlich carcinoma or L-1210. The distribution among various organs of mice was examined after subcuta-neous injection with 3H-formycin or 3H-formycin B. On the basis of radioactivity , formycin shows high concentrations in spleen and kidney, and formycin B is found in peritoneum, urinary bladder, kidney and spleen. By testing the effect on X. oryzae, low antibacterial activity was shown in various organs. When the lethal dose of formycin was injected in dogs, liver damage was found. Formycin B gives a marked reduction in white blood cells, though this reduction is recovered. Formycin inhibits Ehrlich carcinoma in mice and mouse leukemia L-1210, but formycin B does not show any inhibition of these animal tumors. The toxicity of formycin to mice is relatively slight and that of formycin B is extremely small. Both formycin and formycin B inhibit multiplication of influenza At virus in cells of chick chorioallantoic membrane1*2). Thus, formycin has shown interesting antitumor activity, and formycin B antiviral effects. As shown in a paper reporting the antitumor effect of bleomycin A3>4), informa tion of distribution of an antitumor substance in various organs is helpful in finding-sensitive tumors. Therefore, the distribution of formycin and formycin B in various à"organs was examined. In this paper, the antitumor effect, distribution in various organs and toxicities of formycin and formycin B are reported.
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