[Tularemia live vaccine as a modifier of tumorigenesis and carcinogenesis].
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Biomedical subjects
Publications and source records attributed to A K Nersesian.
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DNA comet assay (CA), gel electrophoresis of single cells, is effective in evaluating the genetic (genotoxic) effects of endogenous and exogenous agents. CA was used to study the extent of spontaneous or UV-induced DNA damages in the leukocytes in two groups at genetic risk: in Chernobyl accident liquidators and patients with familial Mediterranean fever (FMF). There was a significant increase in the number of UV-induced and excision repair-mediated DNA breaks in both risk groups as compared to control samples. The spontaneous extent of DNA breaks in the cells of the liquidators and FMF patients were similar to those in the controls. The extent of oxidative DNA damages detected during incubation with the endonuclease enzymes formamidopyrimidine glycosylase and endonuclease III were also determined in FMF patients. There were no statistically significant differences in the extent of oxidative DNA damage in the cells of FMF patients as compared to the controls. The findings give grounds to recommend CA for biomonitoring of genotoxic effects.
The anticlastogenic effect of the herbal preparation Loshtak on rats and mice was tested using the same scheme of treatment and doses of the preparation as are employed in medical practice. It was shown that intragastric administration of Loshtak results in a statistically significant decrease in the clastogenic effect of cyclophosphamide injected 48 h after the end of treatment with Loshtak. High doses of Loshtak did not induce any increase in the number of micronuclei in mouse bone marrow cells. Possible mechanisms responsible for the anticlastogenic effect of Loshtak are discussed.
The influence of human umbilical cord extract (HUGE) on mutagenesis induces by cyclophosphamide in mice bone marrow cells was studied. It was shown that HUGE had no clastogenic property and decreased significantly the number of micronuclei in bone marrow cells of mice during 5 days after the last HUGE infection. We suppose that the antimutagenic effect is connected with interferon induction by HUGE.
The study was concerned with the evaluation of effect of the extract of a human fetal organ, the umbilical cord, on development and growth of such transplantable tumors as Ehrlich's ascites tumor, sarcoma 37, sarcoma 180 and Zajdela's hepatoma as well as of dimethylbenzanthracene- and benzo(a)pyrene-induced cancer. In a subgroup of animals who had been vaccinated once or twice prior to inoculation of cells, a significant inhibition of growth of tumors of all the histologies except sarcoma 180 was observed alongside with a decrease in tumor incidence and partial resorption of ascitic fluid. Preliminary vaccination of rats interfered with dimethylbenzanthracene- and benzo(a)pyrene-induced carcinogenesis reducing tumor incidence and assuring longer latent period and slower progression of cancer.
The current data from literature on the mutagenicity of carcinogens of natural origin are reviewed. A high correlation between carcinogenicity and mutagenicity of this group of agents is established.
The influence of sea-buckthorn oil on cyclophosphamide, farmorubicin and dioxadet mutagenicity was studied. The oil decreased significantly the cytogenetic action of cyclophosphamide and farmorubicin, but not of dioxadet action. Possible mechanisms of antimutagenic action of the oil are discussed.
Antitumor and cytogenetic activities of 4-epi-doxorubicin (EDR), an anthracycline antibiotic, were studied on female Wistar rats with transplantable ascitic ovary tumor (OT). It was shown that after a single administration in a dose of 3 mg/kg, EDR prolonged the average lifespan of the tumor-bearing rats by 213.4 per cent as compared to that in the controls. The maximum number of the aberrant cells in the bone marrow was observed 24 hours after injection of EDR. In 6 day it decreased to the control level. The maximum increase in the number of the OT aberrant cells was recorded 2 days after EDR injection and even in 10 days the number of the aberrant cells amounted to 20.2 +/- 1.3 per cent. It is suggestive of a high selective action of EDR and relation between the EDR antitumor activity and the disturbances in the chromosomal apparatus of the OT cells.
The current literature data on mutagenicity of human carcinogens of natural origin are reviewed. The high correlation is established between carcinogenicity and mutagenicity of this group of agents, all 10 agents are active in the Ames assay or in the cytogenetic tests, 7 of them are mutagenic in the Ames test and 8 in cytogenetic assays.
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Cytogenetic disturbances due to cytostatic preparations--cyclophosphamide and methylnitrosourea--applied as single or ten-times administrations in different doses have been studied for rats immunized with tularemia live dried vaccine. It is established that with the application of these preparations to immunized animals the quantity of chromosomal aberrations in myelokaryocytes decreased from 1.4 to 2.2 times, compared with that in non-immunized animals.
It is established that rat immunization with tularemia living vaccine inhibits Pliss lymphosarcoma growth and increases the life duration to tumour bearing animals. In tests with Zajdela ascitic hepatoma in 1/3 of the immunized animals ascites were not formed and the rats lived 150 days before they were killed.
The living tularemia vaccine is studied for its effect on rat tumours and chromosome aberrations in bone marrow cells during 3,4-benz(a)pyrene injection (BP). It is established that a single epicutaneous vaccination of rats decreases the incidence of BP-induced tumours, prolongs the latent period and reduces the mean weight of tumours as well as lowers the number of myelocaryocytes with chromosome aberrations when BP is administered 15 days after immunization. 125 days after a single subcutaneous injection of BP in a dose of 4 mg the tumours appeared in 57% of animals and in 35% of preliminarily immunized animals. 24 h after intraperitoneal administration of 4 mg of BP the immunized rats revealed a 35% decrease in the amount of chromosome aberrations in myelocaryocytes as compared to the nonimmunized rats.
The paper deals with a study of the effect of a single challenge with living tularemia vaccine on the growth of such transplantable tumors as Zajdela's hepatoma, Pliss' lymphosarcoma, Walker's carcinosarcoma, Schwetz' erythromyelosis and sarcoma 45 in Wistar rats. Immunization was followed by a significant (37.2-86%) inhibition of the rate of growth of the said tumors. Ascites was detected in half the vaccinated animals of Zajdela's hepatoma series, this being matched by 100% in controls.
Immunization with tularemic live dry vaccine administered singularly to Wistar rats skin has been studied for its effect on mutagenicity induced after whole-body X irradiation. The analysis has shown that cytogenetic disturbance induced after X irradiation with doses of 0.5 Gy and 1.0 Gy in immunized animals significantly decreases as compared to nonimmunized animals.
Immunization of Wistar rats with tularemic vaccine has been studied for its influence on the cytogenetic effect of adryblastine and pharmorubicyn. It is shown that the number of aberrant metaphases considerably decreases in the myelocaryocytes of vaccinated rats. Antimutagenic effect is induced by the influence of tularemic vaccine on the metabolic activation processes of antibiotics and, possibly, by an increase of the activity of antioxidative enzymes in the rat organism.
A single epicutaneous vaccination of Wistar rats with tularemic live vaccine 15 days before X-irradiation with doses of 6.0, 8.0 and 2.0 + 6.0 Gy was shown to increase their radioresistance. With higher doses (up to 8.0 Gy) the effect of the vaccine was less pronounced.