Search PubMed⌕ Search

Biomedical subjects

B Toth

Publications and source records attributed to B Toth.

At least 91 records · Page 5Linked to original sources

Reversal of the toxicity of hydrazine an analogues by pyridoxine hydrochloride.

Single subcutaneous injections of each of five substituted hydrazines were given alone and jointly with pyridoxine hydrochloride (PH) to Swiss mice. The convulsive, toxic, and lethal effects of four compounds--methylhydrazine (MH), ethylhydrazine hydrochloride (EH), n-butylhydrazine hydrochloride (BH), and beta-N-[gamma-L(+)-glutamyl]-4-hydroxymethylphenylhydrazine--were successfully prevented by administering PH before and/or after injection. The toxic symptoms caused by N-methyl-N-formylhydrazine (MFH) were, however, only slightly inhibited by this vitamin.

Animals↗

Formation of methylhydrazine from acetaldehyde N-methyl-N-formylhydrazone, a component of Gyromitra esculenta.

Gyromitrin, acetaldehyde N-methyl-N-formylhydrazone, is a toxin present in edible wild mushroom Gyromitra esculenta. At 37 degrees under different acidic conditions (pH 1 to 3), mimicking the milieu of human stomach, gyromitrin is converted to methylhydrazine, a known tumor inducer in mice and hamsters, through an intermediate, N-methyl-N-formylhydrazine. In addition, methylhydrazine is formed in the mouse stomach after p.o. administration of gyromitrin. These findings imply that consumption of G. esculenta could present a carcinogenic, as well as an acutely toxic, health hazard.

Animals↗

Induction of tumors in mice with the herbicide succinic acid 2,2-dimethylhydrazide.

A solution of 2% succinic acid 2,2-dimethylhydrazide was given continuously in the drinking water of 6-week-old randomly bred albino mice for the remainder of their lives. The treatment gave rise to tumors of blood vessels, lungs, and kidneys. The tumor incidences in these tissues in the controls were 6, 18, and 0%, whereas in the treated groups the corresponding tumor incidences were 73, 73, and 5%. Light microscopic examination revealed typical angiomas and angiosarcomas of blood vessels, adenomas and adenocarcinomas of lungs, and adenomas of kidneys. The study thus demonstrates the tumorigenicity of the herbicide, succinic acid 2,2-dimethylhydrazide. Since the residues of this chemical occur in fruit, the human population is exposed to it. The environmental implication of this finding and the fact that the hydrazines as a class have tumorigenic properties are discussed.

Adenocarcinoma↗

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

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 significanly 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.

Animals↗

Photochemically induced cross-links between DNA and alcohol dehydrogenase or salmine, respectively.

Model experiments with two structurally different proteins (alcohol dehydrogenase and salmine) show that glycine, alanine, and tyrosine are by far more frequently involved in photochemically induced cross-link formations with DNA than is cysteine. The yields for cross-link formation of thymidine with salmine (cysteine-free) are about as high as those with alcohol dehydrogenase (athiol protein).

Alcohol Oxidoreductases↗

Scanning electron-microscopic study of the surface characteristics of neoplastic endothelial cells of blood vessels.

The morphological surface characteristics of neoplastic endothelial cells of blood vessels induced by oral administration of 1,2-dimethylhydrazine dihydrochloride in mice were studied by scanning electron microscopy. The interconnecting vascular channels were lined by malignant endothelial cells which formed bridges, cord-like structures and had extended cytoplasmic processes which made the network more intricate. The endothelial cells were often in close approximation to each other and exhibited irregular growth patterns and orientation. The cell surface displayed a rugged, terrace-like microcontour of elevations, depressions, blebs and nodular structures. These findings correlate with the earlier morphological observation obtained by transmission electron microscopy.

Animals↗

Trimethylhydrazine hydrochloride as a tumor inducer in Swiss mice.

A 0.05% solution of trimethylhydrazine hydrochloride (TMH) administered for a lifetime in drinking water to outbred Swiss albino mice, beginning at 6 weeks of age, induced tumors of blood vessels, lungs, and kidneys. The tumor incidences in these tissues in untreated controls were 5,22 and 0%, whereas in the treated groups the corresponding tumor incidences increased to 85, 44, and 6%, respectively. Histopathologically, tumors were classified as angiosarcomas of blood vessels and adenomas of the lungs and kidneys. The study thus demonstrated the tumorigenicity of TMH. Contrary to expectation, the chemical structure modification apparently failed to alter qualitatively the tumorigenic response.

Adenoma↗

Tumorigenicity of tetramethylhydrazine hydrochloride in Swiss mice.

Tetramethylhydrazine hydrochloride (TEMH) was administered in drinking water as a 0.125% solution to randomly bred Swiss mice for life beginning at 6 weeks of age. As a result of treatment, the incidence of blood vessel tumors rose from 5 to 96% in females and from 6 to 88% in males, while that of lung tumors increased from 21 to 36% in females and from 23 to 28% in males, as compared with untreated controls. The increased incidence of blood vessel tumors, but not of lung neoplasms, was statistically significant. Histopathologically, the tumors exhibited the characteristics of angiomas and angiosarcomas of blood vessels and adenomas of the lung. The investigation proved for the first time the tumorigenicity of TEMH. The possible role of increased methyl substitution on hydrazine in tumorigenesis was also discussed, as well as hydrazine derivatives as a tumor-producing class.

Adenoma↗

Production of intestinal and other tumours by 1,2-dimethylhydrazine dihydrochloride in mice. II. Scanning electron microscopic and cytochemical study of colonic neoplasms.

Thum of colon induced by repeated subcutaneous injections of 1,2-dimethyl-hydrazine dihydrochloride in mice were studied by scanning electron microscopy. In addition, the surface composition of normal and malignant colonic epithelial cells were investigated by ultrastructural cytochemistry. The neoplastic, nodular tumour masses which protruded into the lumen of colon displayed an asymmetrical, irregular growth pattern and surface contour. In contrast to the normal surface structure, the shape of crypt openings in malignant areas was distorted and they were irregularly spaced. Cells varying in size and shape in the intercrypt regions often formed random patterns of elevations and depressions. Microvilli on neoplastic cells were larger, more club-shaped and showed more disorderly arrangement than their normal counterparts. The distribution and quantity of surface acid mucopolysaccharide content and adenosine triphosphatase activity varied considerably from cell to cell in the neoplastic epithelium while they were more uniform in the normal colonic surface cells.

Adenocarcinoma↗

Tumorigenicity of beta-phenylethylhydrazine sulfate in mice.

The continuous lifetime administration of 0.015% beta-phenylethylhydrazine sulfate in the drinking water of Swiss mice, beginning at 6 weeks of age, gave rise to tumors of the lungs and blood vessels. As compared to untreated controls, the incidence of lung tumors rose from 21 to 56% in females and from 23 to 36% in males, while the incidence of vascular tumors increased from 5 to 44% in females and from 6 to 8% in males. Statistically, the increased incidence of tumors of lungs and blood vessels in females appears to be significant. The treatment had no statistically significant effect on the development of tumors in males. Histopathological examination revealed the characteristic appearance of adenoma and adenocarcinoma of the lungs, and angioma and angiosarcoma of blood vessels. This study reports for the first time the tumorigenicity of beta-phenylethylhydrazine sulfate, which is currently used to treat mental depression.

Adenocarcinoma↗

Production of intestinal and other tumors by 1, 2-dimethylhydrazine dihydrochloride in mice. I. A light and transmission electron microscopic study of colonic neoplasms.

Single or ten weekly subcutaneous injection(s) of 1, 2-dimethylhydrazine dihydrochloride were administered separately to Swiss mice. The repeated application gave rise mainly to high incidences of tumors in the large intestine. These neoplasms occurred most frequently in the colorectal area and in cecum adjacent to ileum. Light microscopically, these lesions were classified as polypoid adenomas and adenocarcinomas. Most of the adenocarcinomas were highly invasive, although they metastasized rarely. The fine structure of the malignant cells exhibited features typical of columnar absorptive cells. A distinctive alteration was the disorderly arrangement and abnormal size and shape of the microvilli. In addition, the cells exhibited numerous free ribosomes, little RER, priminent Golgi bodies, and uniformly dispersed nuclear chromatin. Morphologically, the intestinal tumors were similar to those found in man. In addition, the repeated administration of 1, 2-DMH also induced significant incidences of neoplasms in blood vessels, lungs, anus, and kidneys while the single application produced tumors in blood vessels and liver. The main hypotheses attempting to explain the selective induction of large intestinal neoplasms are discussed.

Adenocarcinoma↗

[Early and late effects of the gestational course following commisurotomy].

Early and late effects of pregnancy on the cardio-vascular system and on the outcome of the pregnancy were studied in 82 women after commissurotomies. According to the clinical and instrumental investigations the burden of pregnancy may only be temporary and might cause no demonstrable damage on case of careful supervision of specialists before, during and after pregnancy and if there is a considerate delivery. Due to the higher number of "small for date babies" the fetal perinatal mortality rate and premature births are higher than in the general population. The higher incidence of "small for date babies" seems to be related to a decrease of the function of placenta in cases of premature delivery. Further improvement of matermal and foetal results is expected from perfecting diagnostic methods and from a better coordination of the team work of heart surgeons, cardiologists and gynaecologists.

Abortion, Threatened↗

Sex dependent toxicity of four chemicals.

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.

Animals↗

Autoradiographic studies on the distribution of 14C-1,2-dimethylhydrazine dihydrochloride and its effect on DNA synthesis in Swiss mice.

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.

Administration, Oral↗