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Biomedical subjects

D Sh Beniashvili

Publications and source records attributed to D Sh Beniashvili.

At least 19 recordsLinked to original sources

[Induction of tumors of the sympathetic nervous system in rats].

Benign (ganglioneuromas in 6 rats) and malignant (ganglioneuroblastomas--4) tumors and neuroblastomas (7) were induced in 17 animals by a single dose of 80 mg/kg ethylnitrosourea injected on days 18-19 of gestation. The animals were exposed to continuous lighting during gestation and lactation. Tumors of the sympathetic nervous system were at different stages of maturity. Since most tumors were located along the sympathetic trunk of the mediastinum and retroperitoneal cavity and because of their certain morphological features, such neoplasms may be regarded as an adequate model of similar tumors in children.

Animals↗

Biomarkers of individual susceptibility to carcinogens: application for biological monitoring.

In order to develop new markers of individual susceptibility to various human carcinogens, we studied some parameters of formation and metabolism of carcinogens, as well as DNA adducts formation and DNA repair in animals and humans. Following an i.p. administration of benzo(a)pyrene (BP) to the rats, levels of urinary excretion of BP-7,8-diol correlated with tumour latency. A high correlation was found between excretion of this metabolite and BP-DNA adducts level in the liver. Healthy smokers excreted higher quantities of BP-7,8-diol, than smoking lung cancer patients, thus confirming the suggestion on existence of cancer-prone phenotype. N-nitroso compounds formed most efficiently in stomach juice of children with superficial gastritis who therefore could be at high risk of stomach cancer. N-ethyl-N'-nitro-N-nitrosoguanidine induced stomach cancer earlier in monkeys with a low level of DNA repair enzyme, O6-alkylguanine-DNA alkyltransferase (AGT) in gastric mucosa. Overall, these markers can be helpful in predicting individual susceptibility to carcinogens.

Adult↗

Individual levels of activity of O6-alkylguanine-DNA alkyltransferase in monkey gastric mucosa during chronic exposure to a gastrocarcinogen N-ethyl-N'-nitro-N-nitrosoguanidine.

The activity of a DNA repair enzyme, O6-alkylguanine-DNA alkyltransferase (AGT), was studied in gastric mucosa of 15 Macaca fascicularis monkeys before and during chronic oral exposure to the ethylating carcinogen N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG) in order to investigate possible causes of inter-individual differences in susceptibility to its gastrocarcinogenic effect. A wide range of AGT activity (307-1903 fmol/mg protein, mean 695) was found before treatment and it decreased during the first year of exposure (means 627, 479 and 452 fmol/mg protein respectively at 6, 12 and 18 months after the beginning of the experiment). The carcinogenesis study is under way and to date four monkeys with low initial AGT level in gastric mucosa died of gastric cancer. The relevance of AGT level measurement for prediction of individual susceptibility to ENNG is discussed.

Administration, Oral↗

Biomarkers for individual susceptibility to carcinogenic agents: excretion and carcinogenic risk of benzo[a]pyrene metabolites.

In rats exposed to a single intraperitoneal dose of 200 mg/kg of the environmental carcinogen benzo[a]pyrene (BP) in sunflower oil, significant individual variations in excretion of the BP activation (BP-7,8-diol) and deactivation (3-OH-BP) derivatives were found. Most rats developed peritoneal sarcomas. Only the levels of BP-7,8-diol excreted in the urine correlated directly with the latency of tumor formation. After a similar exposure to a dose of 100 mg/kg BP, Macaca fascicularis monkeys excreted smaller quantities than rats of both metabolites. After rats were given 10 intraperitoneal injections each of 10 mg/kg of BP in a water-lipid emulsion, the excreted levels of both metabolites after the first, fifth, and tenth injection were lower than those of the rats that received 200 mg/kg. BP metabolites were also detected in the urine of lung cancer patients who were heavy smokers. The applicability of monitoring the excretion of the BP metabolites to predicting individual cancer risk is discussed.

Animals↗

[Esophageal tumor induction in monkeys].

The experiment used eight monkeys who had received such esophagotropic carcinogens as ethyl ester of N-nitrososarcosine and methyl-N-benzyl-N-nitrosamine. The animals were followed for 4 years. The former agent failed to induce cancer where as 3 monkeys who had received methyl-N-benzyl-N-nitrosamine in the total dose of 600, 625 and 720 mg developed esophageal tumors (papilloma-2 and squamous cell carcinoma-1) at days 527, 725 and 880 after the start of treatment. The biological and histological features of the tumors were close to those of their human counterparts.

Animals↗

[The individual characteristics of the activity of the DNA-repair enzyme O(6)-alkylguanine-DNA alkyltransferase in the stomach of monkeys exposed to the gastric carcinogen N-ethyl-N1-nitro-N-nitrosoguanidine].

Variations in the activity of a DNA repair enzyme 0(6)-alkylgianine-DNA alkyltransferase (AGT) were studied in gastric mucosa samples obtained from 15 M. fascicularis monkeys chronically exposed to a gastrocarcinogen N-ethyl-N'-nitro-N-nitrosoguanidine. Marked interindividual difference in the enzyme activity before and in the course of the exposure was observed. The value of AGT activity assay to predict individual susceptibility to alkylating carcinogens is discussed.

Animals↗

[Spontaneous tumors in monkeys].

The analysis of 783 monkeys has revealed all varieties of malignant and benign tumors, being typical of human beings. These were most frequently tumours of the digestive tract and hemopoietic organs. The highest tumour incidence was observed in the older age groups. Spontaneous tumours were found more often in macaques and baboons, the malignant epithelial tumours prevailing.

Age Factors↗

[Induction of renal tumors in monkeys as a result of probable prenatal effects of 1,2-dimethylhydrazine].

Prenatal treatment with 1,2-dimethylhydrazine induced embryonal nephroma in two out of six monkeys. In one case, tumor of the right kidney disseminated to the lower lobes of both lungs. Induced embryonal nephroma of monkey proved similar to Wilms' tumor, a frequent pediatric pathology, in terms of histologic pattern, duration of latent period and clinical course.

1,2-Dimethylhydrazine↗

Induction of gastric cancer in monkeys by N-methyl-N-nitro-N-nitrosoguanidine (MNNG).

N-methyl-N-nitro-N-nitrosoguanidine (MNNG) was administered to 9 Macaca fascicularis monkeys (7 males and 2 females) through a tube at a dose of 40 mg/kg body weight 3 times a month. Tumors of the pyloric part of the stomach were observed in 2 male monkeys after MNNG doses of 800 and 848 mg/kg body weight, with a latent period of tumor development of 49 and 50 weeks, respectively. Histologically, in one case the tumor was a solid carcinoma, and in the other it had a mixed structure showing alternating solid and signet ring cell carcinoma areas.

Animals↗

[Development of experimental peripheral nerve tumors in hormonal imbalance].

According to the data obtained by the authors, some modifying factors, and in particular artificial disorders of hormonal balance in rats, influence the realization of the blastomogenic effect of methylnitrosourea. The results of these studies indicate that the manifestation and the development of tumors in the peripheral nerves occurs more rapidly and easier in experimental hypothyrosis due to a daily administration of anti-thyroid drugs (merkazolyl) and an estrogenation of the organism of animals by a monthly subcutaneous suturation of sinestrol pills. In castration and administration of thyroid hormones (thyroidin) the amount of experimental neurogenic newgrowths decreases with an extension of the latent period of their development.

Animals↗

[Ultrastructure of tumors arising from Schwann cells].

Ultrastructural changes have been studied using 67 tumors originated from the Schwann cells. Tumors were induced by means of methylnitrosourea injection with a week intervals. Both benign (fascicular and reticular) and malignant neurinomes were obtained. Main morphological changes were found in the Schwann cells. The tumor cell ultrastructure appeared to be definetely related to the degree of the tumor maturity. The results obtained may suggest that the fine structure of neurogenic tumors is also characteristic of their normal prototype--the Schwann cells.

Animals↗