Tumorigenic effects of chronic administration of benzylhydrazine dihydrochloride and phenylhydrazine hydrochloride in Swiss mice

  • B. Toth
  • H. Shimizu
Original Papers


Separate solutions of 0.015% benzylhydrazine dihydrochloride and 0.01% phenylhydrazine hydrochloride were given continuously in the drinking water of 6- and 5-week-old randomly bred Swiss mice for the remainder of their life. The consumption of benzylhydrazine dihydrochloride significantly increased the lung tumor incidence from 21 to 42% in the females, while in phenylhydrazine hydrochloride-treated mice, the incidence of blood vessel tumors rose significantly from 5 to 22% in females and from 6 to 20% in males, as compared with the controls. Histopathologically, the tumors were classified as adenomas and adenocarcinomas of lungs and angiomas and angiosarcomas of blood vessels.

The study thus proves for the first time the tumorigenicity of benzylhydrazine dihydrochloride. It also confirms the tumor inducing ability of phenylhydrazine hydrochloride, which is used in medicine for treatment of polycythemia vera.


Adenocarcinoma Adenoma Blood Vessel Drinking Water Lung Tumor 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. Armitage,P.: Statistical Methods in Medical Research, pp.135–138. Oxford, England: Blackwell Scientific Publications, Ltd. 1971Google Scholar
  2. Andervont,H.B., Shimkin,M.B.: Biologic testing of carcinogens. II. Pulmonary-tumor induction technique. J. nat. Cancer Inst. 1, 225–239 (1940)Google Scholar
  3. Beaven,G.H. and White,J.C.: Oxidation of phenylhydrazines in the presence of oxyhaemaglobin and the origin of Heinz bodies in erythrocytes. Nature 173, 389–391 (1954)Google Scholar
  4. Bhai,I., Sivakumar,B., Nath,M.C.: Studies on protein synthesis and vitamin B12 status in phenylhydrazine treated rats. J. Vitamin. 15, 222–225 (1969)Google Scholar
  5. Clayson,D.B., Biancifiori,C., Milia,U., Giornelli-Santilli,F.E.: The induction of pulmonary tumours in BALB/c/Cb/Se mice by derivatives of hydrazine. In Lung Tumours in Animals, ed. L. Severi, pp. 869–880. Proc. Quadrenn. Conf. on Cancer, Perugia, Italy (1966)Google Scholar
  6. Eberson,L.E., Persson,K.: Studies on monoamine oxidase inhibitors. I. The autooxidation of β- phenylisopropylhydrazine as a model reaction for irreversible monoamine oxidase inhibition. J. med. pharm. Chem. 5, 738–752 (1962)Google Scholar
  7. Eichhorn,G.L. (ed.): Inorganic biochemistry. Vol.2, pp.769–775. New York: Elsevier Scientific Publ. Co. 1973Google Scholar
  8. Food Protection Committee. Food and Nutrition Board. Problems in the evaluation of carcinogenic hazards from the use of food additives. National Research Council Publication No. 749, 26 pp. Washington, D. C.: National Academy of Sciences 1960Google Scholar
  9. Hecht,S.S., Schmeltz,I., Hoffmann,D., Wynder,E.L.: Chemical studies on tobacco smoke. XL. Identification of carcinogens in tobacco. Presented at a workshop of the Third World Conference on Smoking and Health, New York (1975)Google Scholar
  10. Kato,R., Takanaka,A., Shoji,H.: Inhibition of drug metabolizing enzymes of liver microsomes by hydrazine derivatives in relation to their lipid solubility. Jap. J. Pharmacol. 19, 315–322 (1969)Google Scholar
  11. Kelly,M.G., O'Gara,R.W., Yancey,S.T., Gadekar,K., Botkin,C., Oliverio,V.T.: Comparative carcinogenic of N-isopropyl-α-(2-Methylhydrazino)-p-Toluamide HCl (Procarbazine hydrochloride), its degradation products, other hydrazines, and isonicotinic acid hydrazide. J. nat. Cancer Inst. 42, 337–344 (1969)Google Scholar
  12. Levenberg,B.: Structure and enzymatic clevage of agaritine, a new phenylhydrazide of α-glutamic acid isolated from Agaricaceae. J. biol. Chem. 239, 2267–2273 (1964)Google Scholar
  13. List,P.H., Luft,P.: Nachweis und Gehaltsbestimmung von Gyromitrin in frischen Lorcheln. Arch. Pharm. 302, 143–146 (1969)Google Scholar
  14. Liu,Y.Y., Schmeltz,I., Hoffmann,D.: Chemical studies on tobacco smoke. Quantitative analysis of hydrazine in tobacco and cigarette smoke. Anal. Chem. 46, 885–889 (1974)Google Scholar
  15. Roe,F.J.C., Grant,G.A., Millican,D.M.: Carcinogenicity of hydrazine and 1,1-dimethylhydrazine for mouse lung. Nature 216, 375–376 (1967)Google Scholar
  16. Satoh,T.: Inhibitory effects of phenylhydrazine on the induction of tryptophan pyrrolase in rats. Enzym. biol. clin. 11, 268–276 (1970)Google Scholar
  17. The Merck Index. 8th ed., Rahway, N. J. (1968)Google Scholar
  18. Toth,B.: Investigations on the relationship between chemical structure and carcinogenic activity of substituted hydrazines. Proc. Amer. Ass. Cancer Res. 12, 55 (1971)Google Scholar
  19. Toth,B.: A toxicity method with calcium cyclamate for chronic carcinogenesis experiments. Tumori 58, 137–142 (1972)Google Scholar
  20. Toth,B.: 1,1-Dimethylhydrazine (unsymmetrical) carcinogenesis in mice. Light microscopic and ultrastructural studies on neoplastic blood vessels. J. nat. Cancer Inst. 50, 181–194 (1973)Google Scholar
  21. Toth,B.: Synthetic and naturally occurring hydrazines as possible cancer causative agents. Cancer Res. 35, 3693–3697 (1975)Google Scholar
  22. Toth,B., Magee,P.N., Shubik,P.: Carcinogenesis study with dimethylnitrosamine in orally treated adult and subcutaneously injected newborn BALB/c mice. Cancer. Res. 24, 1712–1721 (1964)Google Scholar
  23. Toth,B., Nagel,D., Kupper,R.: Investigations on tumorigenic activities of four substituted hydrazines. pp.62–63. Abstracts and Programme, Third Meeting of Europ. Assoc. Cancer Res., Nottingham, England (1975)Google Scholar
  24. Toth,B., Rappaport,H., Shubik,P.: The influence of dose and age on the induction of malignant lymphomas and other tumors by 7,12-dimethylbenz(a)anthracene in Swiss mice. J. nat. Cancer Inst. 30, 723–741 (1963)Google Scholar
  25. Toth,B., Shimizu,H.: 1-Carbamyl-2-phenylhydrazine tumorigenesis in Swiss mice. Morphology of lung adenomas. J. nat. Cancer Inst. 52, 241–251 (1974)Google Scholar
  26. Toth,B., Wilson,R.B.: Blood vessel tumorigenesis by 1,2-dimethylhydrazine dihydrochloride (symmetrical). Gross, light, and electron microscopic descriptions. I. Am. J. Pathol. 64, 585–600 (1971)Google Scholar

Copyright information

© Springer-Verlag 1976

Authors and Affiliations

  • B. Toth
    • 1
  • H. Shimizu
    • 2
  1. 1.The Eppley Institute for Research in Cancer University of Nebraska Medical CenterOmahaUSA
  2. 2.Department of Public HealthJikei University School of MedicineTokyoJapan

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