218 



DESCRIPTIONS OF ANTIBIOTICS 



transmissible resistance (25). Inhibits purine syn- 

 thesis in normal and tumor cells of animals and E . 

 coli (20, 21). Inhibits incorporation of formate 

 into the nucleic acids of sarcoma 180, adenocar- 

 cinoma E0771, as well as normal tissues such as 

 the intestine and liver (mice) (8). 



Toxicity: MLD (mice) 62 to 124 mg per kg in- 

 travenously (16); 25 mg per kg per day in rats 

 produces lesions of the pancreas, liver, and kid- 

 ney, as well as depletion of cellular elements in 

 the bone marrow, reticulocytopenia, and granulo- 

 cytopenia (10). Administered during the 8th to 

 12th day of gestation, may cause fetal resorption 

 and teratogenic effects in rats, but does not have 

 adverse effects on the mother even after five con- 

 secutive abortions, delay mating, or harm subse- 

 quent litters. The fetus is directly affected, not 

 the ovaries, placenta, or pituitary (24). In chick 

 embryos, azaserine given from the 3rd to 5th day 

 of incubation causes skeletal abnormalities and 

 developmental defects (2.3). Toxic to the canine 

 fetus (26). In human beings, causes mouth lesions, 

 anorexia, apathy, nau.sea, vomiting, and some 

 leukopenia (14). Growth of roots (but not shoots) 

 of cucumber, barley, and flax seedlings is inhibited 

 by <3 fig per ml (15). 



Utilization: Some beneficial results in Hodgkin's 

 disease, chronic lymphatic leukemia, and acute 

 leukemia in children, liut protjably will be used, if 

 at all, only in combination with other drugs (14, 

 31). 



References: 



1. Stock, C. C. et al. Nature, London 17.'?: 



71-72, 1954. 



2. Ehrlich, J. et al. Nature, London 173: 72, 



1951. 



3. Bartz, Q. R. et al. Nature, London 



72, 1954. 



4. Fusari, S. A. et al. J. Am. Chem. Soc. 



2878-2881, 1954. 



5. Fusari, S. A. et al. ,1. Am. Chem. Soc. 76: 



2881-2883, 1954. 



6. Nicolaides, E. D. et al. J. Am. Chem. Soc. 



76: 2887-2891, 1954. 



7. Burchenal, J. H. et al. Proc. Soc. Exptl. 



Biol. Med. 86: 891-893, 1954. 



8. Skipper, H. E. et al. Federation Proc. 13: 



298-299, 1954. 



9. Ehrlich, J. et al. Federation Proc. 13: 351, 



1954. 



10. Sternberg, S. S. f/ a/. Federation Proc. 1.3: 



444, 1954. 



11. Maxwell, R. E. and Nickel, V. S. Science 



120: 270-271, 1954. 



12. Coffey, G. F. et al. Antibiotics tt Chemo- 



therapy 4: 775-791, 1954. 



173: 



76: 



13. Stock, C. C. et al. Al)str. 12.5th :\Ieeting 



Am. Chem. Soc. 12M, 1954. 



14. Ellison, R. R. et al. Cancer 7: 801-814, 



1954. 



15. Norman, A. G. Science 121: 213-214, 



1955. 



16. Nitta, K. e/ a/. J. Antibiotics (Japan) 8A: 



120-125, 1955. 



17. Gots, J. S. et al. Biochim. et Biophys. 



Acta 17: 449-450, 1955. 



18. Sugiura, K. (cjuoted in Stock, C, C. et al. 



Acta Unio Intern, contra Cancrum 11: 

 186-193, 1955). 



19. Sugiura, K. and Stock, C. C. Proc. Soc. 



Exptl. Biol. Med. 88: 127-129, 1955. 



20. Bennett, L. L., Jr. et al. Arch Biochem. 



Biophys. 64: 423-436, 1956. 



21. Tomisek, A. J. et al. Arch. Biochem. Bio- 



phys. 64: 437-455, 1956. 



22. Nakamura,M. Nature, London 178:1119- 



1120, 1956. 



23. Karnovsky, D. A. et al. Proc. Am. Assoc. 



Cancer Research 2: 101, 1956. 



24. Thiersch, J. B. Proc. Soc. Exptl. Biol. 



Med. 94: 27-32, 1957. 



25. Potter, M. and Law, L. W. J. Natl. Cancer 



Inst. 18: 413-442, 1957. 



26. Friedman, M. H. J. Am. Vet. Med. Assoc. 



130: 159-162, 1957. 



27. Tomiiiek, A. etal. Plant Physiol. 32:7-10, 



1957. 



28. Sugiura, K. Ann. N. Y. Acad. Sci. 76: 575- 



585, 1958. 



29. Sassenrath, E. N. Ann. N. Y. Acad. Sci. 



76: 601-609, 1958. 



30. Ammann, C. A. and Safferman, R. S. Anti- 



biotics & Chemotherapy 8: 1-7, 1958. 



31. Duvall, L. R. Cancer Chemotherapy Rept. 



pp. 65-86, May, 1960. 



Azoniyciii 



Produced by: Nocardia mesenterica (2, 6), Strep- 

 tomyces eurocidicus (4), and a Streptomyces sp. re- 

 sembling S. eurocidicus. N. mesenterica also pro- 

 duces me.senterin and Antibiotic 446. S. eurocidicus 

 also produces tertiomycin and eurocidin. The 

 Streptomyces sp. resembling S. eurocidicus also 

 produces methymycin (9). 



Synonym: Antibiotic llA (9). 



Method of extraction: Broth-filtrate extracted 

 with ethyl acetate at pH 2.0; pH of extract ad- 

 justed to 7.0. Concentration in vacuo. Crude crys- 

 tals form on cooling. Recrystallization from meth- 

 anol or ethanol (1). 



Chemical and physical properties: Acidic sub- 

 stance. White needle-shaped crystals (4) or color- 



