Skip to main content
Log in

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

  • Original Papers
  • Published:
Zeitschrift für Krebsforschung und Klinische Onkologie Aims and scope Submit manuscript

Summary

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Armitage,P.: Statistical Methods in Medical Research, pp.135–138. Oxford, England: Blackwell Scientific Publications, Ltd. 1971

    Google Scholar 

  • 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 

  • 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 

  • 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 

  • 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 

  • 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 

  • Eichhorn,G.L. (ed.): Inorganic biochemistry. Vol.2, pp.769–775. New York: Elsevier Scientific Publ. Co. 1973

    Google Scholar 

  • 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 1960

    Google Scholar 

  • 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)

  • 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 

  • 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 

  • 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 

  • List,P.H., Luft,P.: Nachweis und Gehaltsbestimmung von Gyromitrin in frischen Lorcheln. Arch. Pharm. 302, 143–146 (1969)

    Google Scholar 

  • 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 

  • 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 

  • Satoh,T.: Inhibitory effects of phenylhydrazine on the induction of tryptophan pyrrolase in rats. Enzym. biol. clin. 11, 268–276 (1970)

    Google Scholar 

  • The Merck Index. 8th ed., Rahway, N. J. (1968)

  • 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 

  • Toth,B.: A toxicity method with calcium cyclamate for chronic carcinogenesis experiments. Tumori 58, 137–142 (1972)

    Google Scholar 

  • 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 

  • Toth,B.: Synthetic and naturally occurring hydrazines as possible cancer causative agents. Cancer Res. 35, 3693–3697 (1975)

    Google Scholar 

  • 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 

  • 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)

  • 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 

  • 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 

  • 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 

Download references

Author information

Authors and Affiliations

Authors

Additional information

This study was supported by Public Health Service Contract PH43-NCI-E-68-959 from the National Cancer Institute, NIH

Rights and permissions

Reprints and permissions

About this article

Cite this article

Toth, B., Shimizu, H. Tumorigenic effects of chronic administration of benzylhydrazine dihydrochloride and phenylhydrazine hydrochloride in Swiss mice. Z. Krebsforsch. 87, 267–273 (1976). https://doi.org/10.1007/BF00506499

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00506499

Keywords

Navigation