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.
Similar content being viewed by others
References
Armitage,P.: Statistical Methods in Medical Research, pp.135–138. Oxford, England: Blackwell Scientific Publications, Ltd. 1971
Andervont,H.B., Shimkin,M.B.: Biologic testing of carcinogens. II. Pulmonary-tumor induction technique. J. nat. Cancer Inst. 1, 225–239 (1940)
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)
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)
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)
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)
Eichhorn,G.L. (ed.): Inorganic biochemistry. Vol.2, pp.769–775. New York: Elsevier Scientific Publ. Co. 1973
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
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)
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)
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)
List,P.H., Luft,P.: Nachweis und Gehaltsbestimmung von Gyromitrin in frischen Lorcheln. Arch. Pharm. 302, 143–146 (1969)
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)
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)
Satoh,T.: Inhibitory effects of phenylhydrazine on the induction of tryptophan pyrrolase in rats. Enzym. biol. clin. 11, 268–276 (1970)
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)
Toth,B.: A toxicity method with calcium cyclamate for chronic carcinogenesis experiments. Tumori 58, 137–142 (1972)
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)
Toth,B.: Synthetic and naturally occurring hydrazines as possible cancer causative agents. Cancer Res. 35, 3693–3697 (1975)
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)
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)
Toth,B., Shimizu,H.: 1-Carbamyl-2-phenylhydrazine tumorigenesis in Swiss mice. Morphology of lung adenomas. J. nat. Cancer Inst. 52, 241–251 (1974)
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)
Author information
Authors and Affiliations
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
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
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00506499