Tumour induction study with n-amylhydrazine hydrochloride in Swiss mice.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to B Toth.
Explore the source record for details and available documents.
Toxicity investigations were conducted with 4 chemicals: hydrazine, 1,2-dimethylhydrazine di HCl, phenylhydrazine HCl and Beta-N-(gamma-L(+)-glutamyl)-4-hydroxymethylphenylhydrazine in Swiss mice. Hydrazine and phenylhydrazine HCl were administered daily in drinking water, the former at 0.01% and the latter at 0.001% concentrations. The 1,2-dimethylhydrazine di HCl and Beta-N-(gamma-L(+)-glutamyl)-4-hydroxymethylphenylhydrazine were given as a single subcutaneous injection at 45 mug and 100 mug/gr. body weight basis, respectively. The findings clearly showed that all four chemicals exerted a stronger toxic effect in male than in female mice. It is, therefore, recommended in similar situations to use different doses of chemicals for each sex in the long-term tumorigenesis studies.
Light microscopic autoradiographic studies were made on the distribution of 14C-1,2-dimethylhydrazine dihydrochloride in Swiss mice and on the effect of 1,2-dimethylhydrazine dihydrochloride on DNA synthesis, using the 3H-thymidine incorporation technique. In the first study, 14C-1,2-dimethylhydrazine dihydrochloride was administered subcutaneously or orally. Large amount of silver grains were found in hepatocytes and substantially lower amount of silver grains observed in the endothelial cells and epithelial cells of colon. In the second study, repeated injections or oral administrations of 1,2-dimethylhydrazine dihydrochloride were given to mice which subsequently received 3H-thymidine treatment. A somewhat higher amount of thymidine incorporation in DNA was noted in the epithelial cells of the colon of subcutaneously and orally treated mice at two occasions and a substantially higher amount in the endothelial cells of blood vessels in liver of mice treated by both routes than in the corresponding controls. In three instances, however, the amount of incorporation decreased; in the hepatocytes and endothelium at 1 week and 24 hr, respectively, after oral treatment, and in the epithelium of the colon at 3 months, after subcutaneous administration. In the mice treated with 1,2-dimethylhydrazine dihydrochloride, a significantly high amount of 3H-thymidine incorporation was observed in the endothelial cells of blood vessel in liver from which tumors later arose, and somewhat high in the hepatocytes in which tumor did not develop. In the epithelial cells of colon, no apparent relationship can be seen between these events. No association was seen in the distribution of 14C-1,2-dimethylhydrazine dihydrochloride and tumor development in various cells.
The various synthetic substituted hydrazines, which cause tumors in animals, are briefly enumerated. To date, 19 of them have proved to be tumorigenic in animals. A number of these chemicals are found today in the environment, in industry, in agriculture, and in medicine, and the human population is exposed to a certain degree to some of them. Hydrazine also occurs in nature in tobacco and tobacco smoke. The three other naturally occurring hydrazine compounds are N-methyl-N-formylhydrazine, which occurs in the wild edible mushroom, Gyromitra esculenta, and beta-N-[gamma-L(+)-glutamyl]-4-hydroxymethylphenylhydrazine and 4-hydroxymethylphenylhydrazine, which are found in the commonly eaten cultivated mushroom, Agaricus bisporus. Tumorigenesis studies with the naturally occurring hydrazines are in progress.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Administration of 0.001% 1,2-dimethylhydrazine dihydrochloride, symmetrical, in the drinking water of 7-week-old randomly bred Swiss mice for the remainder of their lifetime induced blood vessel tumors and enhanced the incidence of lung neoplasms. Ninety-eight percent of the females and 92% of the males developed vascular lesions, whereas among the controls the incidence was 3% in the females and 1% in the males. In addition, the incidence of lung tumors rose from 12 to 44% in the females and from 10 to 24% in the males, as compared with the controls. The occurrence of the vascular tumors in order of decreasing frequency was as follows: muscle, pararenal, fat, liver, parametrial, paraepididymal tissues, etc. Gross, light and electron microscopic examinations of vascular lesions revealed the characteristic appearance of angiosarcomas. The type and extent of macroscopic and histologic involvements of the various tissues by the tumors are presented. The ultrastructural descriptions of hemorrhagic areas, vascular spaces, neoplastic endothelial cells, their cytoplasms and organelles are illustrated in detail.In conclusion, whereas hydrazine enhanced the development of lung tumors, when the dimethyl group was attached to it at symmetrical positions, it evoked vascular tumors. Thus, the present study provides evidence for the possible relationship between chemical structure and tumor induction at specific organ sites.
Explore the source record for details and available documents.