Toxicogenomic Effects in Rat Blood Leukocytes and Chemoprophylaxis of Radiation-Induced Carcinogenesis.

Toxicogenomic parameters were studied in the blood of female rats after exposure to ionizing γ-radiation in a dose of 4 Gy and chemoprophylaxis with α-difluoromethylornithine, eleutherococcus or leuzea extracts, which were used in animals with morphological manifestations of tumor growth under conditions of radiation-induced carcinogenesis. Life-time evaluation of toxicogenomic effects was carried out by express method for measurements of blood nucleotid DNA - fluorescent indication. The level of hyperaneu/polyploidy increased in the blood leukocytes of control rats 30 days after radiation exposure. A significant decrease of genotoxicity as a result of drug treatment in comparison with the number and multiplicity of tumors in irradiated animals was found only in the endocrine and reproductive organs of rats treated by eleutherococcus extract.

Effects of Amygdaline from Apricot Kernel on Transplanted Tumors in Mice.

The effects of amygdaline from apricot kernel added to fodder on the growth of transplanted LYO-1 and Ehrlich carcinoma were studied in mice. Apricot kernels inhibited the growth of both tumors. Apricot kernels, raw and after thermal processing, given 2 days before transplantation produced a pronounced antitumor effect. Heat-processed apricot kernels given in 3 days after transplantation modified the tumor growth and prolonged animal lifespan. Thermal treatment did not considerably reduce the antitumor effect of apricot kernels. It was hypothesized that the antitumor effect of amygdaline on Ehrlich carcinoma and LYO-1 lymphosarcoma was associated with the presence of bacterial genome in the tumor.

Study of Antitumor Activity of Sodium Phenylbutyrate, Histon Deacetylase Inhibitor, on Ehrlich Carcinoma Model.

Antitumor activity of sodium phenylbutyrate was studied on 120 outbred female mice with transplanted Ehrlich ascites carcinoma. The animals received the drug in doses of 400, 800, and 1200 mg/kg with drinking water daily for 21 days. The antitumor effect was evaluated by tumor growth inhibition and lifespan prolongation. Phenylbutyrate in the dose of 800 mg/kg was most effective. The drug inhibited the tumor growth by 71%, prolonged the lifespan of animals by 28, and was low-toxic.

Effects of iron ions and iron chelation on the efficiency of experimental radiotherapy of animals with gliomas.

We evaluated the effect of iron ion chelation on the growth of gliomas and radiotherapy efficiency in tumor-bearing animals. The rats with transplanted glioma-35 received iron-containing water; desferroxamine was injected for metal chelation. Long-term treatment with iron-containing water promoted glioma growth in rats and improved the efficiency of radiotherapy due to combination of apoptosis and ferroptosis. Desferroxamine reduced the efficiency of this treatment and was inessential for the efficiency of radiotherapy alone.

[Effects of iron ion additional introduction in radiation therapy of tumor-bearing animals].

The gender differences of the transplantable glioma-35 growth were revealed in tumor-bearing rats. The effect of mineral iron containing water (ICW) as drinking water was studied during radiation therapy (RT) in tumor bearing male rats. It was shown that ICW used separately had a weak anti cancer effect. The ICW use after irradiation caused no significant changes in hematological reactions as compared with RT only. The mineral water administration before irradiation resulted in the reduction of the supercoiled DNA index on the 1st and 21st day after irradiation, as well as in monocytopeny and a definite decrease in the tumor volume on the 21st day of the experiment as compared with control, which is associated with the ferroptosis effect of ICW. It was established that the reaction peculiarities of the blood DNA structure index in irradiated rats at the early stage of glioma growth may serve an express marker of the efficiency of RT.

[Comparative effects of difluoromethylornithine and tincture of Siberian ginseng root on radiation carcinogenesis and life span in rats].

Influence of alpha-difluoromethylornithine (DFMO) and tincture of Siberian ginseng root (TSGR) on radiation carcinogenesis and life span in rats has been studied. The results of the study demonstrate that DFMO as well as TSGR significantly improved survival and decreased incidence and multiplicity of malignant and benign tumors in rats subjected to ionizing radiation. Beneficial effect on the rat survival rate and anticarcinogenic action of DFMO were more expressed compared with TSGR.

[Inhibitory effect of bioginseng on radiation-induced carcinogenesis in rats].

Influence of bioginseng (biotechnological pharmaceutical drug from ginseng radix culture) on radiation-induced carcinogenesis has been studied. LIO female rats were divided into 3 groups. Rats of the first group (n=25) were used as intact control and weren't exposed to any influence. Rats of the second (n=50) and third (n=50) groups were exposed to single total body gamma-irradiation at a dose of 4 Gy. Animals of the 2nd group weren't exposed to any influence after irradiation, while animals of the 3rd group were given bioginseng with tap water (20 ml/l) until the end of study (438 days). In the control group 22,7% of animals developed tumors. In the 2nd group (irradiated control) 70% of animals were bearing multiple tumors one third of which were malignant. Mammary gland tumors were most frequent. Compared to the 2nd group the 3rd group receiving irradiation and bioginseng demonstrated the decrease in tumor incidence by 24.5% and 2,4 rate of decrease in tumors number. For the malign tumors was observed the decrease by 26.8% and 2,9 times, accordingly. For the mammary tumors the decrease was by 23.0% and 2,0 times, for mammary adenocarcinomas by 23.4% and 3,5 times, accordingly. The incidence and number of endocrine and reproductive organs tumors was 20,9% and 5,6 times, accordingly. Therefore, bioginseng effectively inhibits carcinogenesis induced by ionizing radiation in female rats.

[Effect of additional administration of ferric ion on the life span of irradiated animals].

There were established regularity of early biological reactions, restoration and life span shortening in rats after gamma-irradiation of animals with low (25 and 50 cGy) or 600 cGy doses in combination with various regimen of ferric ions introduction with drinking water (60-63 mg/l).

[The influence of ferromagnetic screening from natural electromagnetic fields on the hematological and toxicogenomic indexes in animals].

The aim of the study was to reveal during 45 days consequences of ferromagnetic screening (FS) on the hematological and toxicogenomic indexes in rats. An express-method of nucleiod DNA content in blood by help fluorescent indication was used for alive quantitative evaluation of the toxicogenomic effects. The FS for both gender rats during 48 hrs resulted in both decreased magnetic field by 4-10 microT1 and leucopenia by 14 day of experiment. The aneu-/polyploidy index in male leucocytes was increased by 48 hr of FS and lasted out to 12-28 days after the screen removal. The leukocyte apoptosis was enhanced in female in 48 hrs only after the FS start.

[Effect of additional administration of iron ions on the efficacy of radiotherapy of glioma-bearing animals].

Our analysis failed to establish any antitumor effect of treatment of rats with transplantable glioma-35 with iron-containing mineral drinking water (ICMW). The latter treatment combined with irradiation (15 Gy) was followed by enhanced genotoxic effect in white blood cells. Post-irradiation administration of ICMW did not influence glioma growth significantly as compared with radiation alone. Pre- and post-iradiation drinking of ICMW resulted in marked leukopenia 24 hrs after exposure as well as to significant decrease in tumor size (20-40 days after of experiment) as compared with control.

[Effect of age and gender on genotoxic and biochemical indexes in animal blood after low doses of radiation-mercury exposures].

The study was executed with the young (4-5 months) and elderly (15-18 months) rats of both gender at the experiment start. The mercury salt was administered into animals with drinking water in 1 mcg/l concentration during 3 months before and 1 month after single X-irradiation with 25 cGy dose. The genotoxic effects in leukocytes were evaluated on the base of the content and structure DNA alterations in 24 hrs and in 1 month after irradiation. The alaninaminotransferase activity and the urea content in serum were determined to evaluate functional status of liver and kidney, respectively. The irradiation of rats receiving mercury with drinking water resulted in increase of the leukocyte DNA content in young male and decrease of the leukocyte quantity in young female at the early terms. At the same time the decrease of monocyte content and the alterations of the blood leukocyte DNA structure were observed in the elderly female. One month after combined exposures the whole leukocyte amount in young females was increased to the intact control level and the leukocytosis was observed in elderly females accompanied by significant condensation of the leukocyte DNA structure. At the same time granulocyte quantity was observed in young males in compare with the intact rats, and the tendency of the increased genotoxicity was lasted out. After combined exposures the functional liver alterations were observed in the highest degree among young male rats (+62%), in approximately identical degree among young and elderly females (+38% and +27%), and practically were absent among elderly males. The absence of the urea concentration increase in the serum of the all experimental group animals in comparison with the intact control rats evidenced, that lesion of kidneys did not take place. So, in despite of the fact that young females revealed sensitivity to the radiation-mercury environment exposure with the low doses in the early term, then they demonstrated the better restoration in compare with the young males and the elderly females. The elderly males were found the least sensitive to the radiation-mercury exposure with low doses among the studied animal groups.

[Effects of ligfol after radiation-mercury exposure in rats of various age].

The study was carried out with the young (4-5 months) and elderly (15-18 months) female and male rats at the experiment start. The mercury salt was administered into animals with drinking water in 1 mcg/l concentration during 3 months before and 1 month after single X-irradiation with 25 cGy dose. The genotoxic effects in leukocytes were evaluated on the base of the content and structure DNA alterations in 24 hrs and in 1 mth after irradiation. The alaninaminotransferase activity in serum was determined to evaluate functional status of liver. A protector intramuscular injection of Ligfol preparation with the 250 mg/kg dose in 24 hrs before irradiation resulted in increase of the blood leukocyte amount, more expressed in 1 mth after irradiation. The standardizing effect of preparation on the leukocyte DNA content is manifested in 1 mth after combined exposure on rats within young male and elderly female. At the same time, Ligfol showed some restoring effect on the alterations of leukocyte supercoiled DNA structure in 1 mth after irradiation within elderly female rats. The preparation showed the standardizing effect on the liver cells in young males injured by radiation-mercury exposures with low doses, however Ligfol had not influence practically on the destruction degree of hepatocytes after similar injury within female young and elderly rats. So, results of the intramuscular Ligfol injection is manifested at least during 1-2 mths; the young rats of both gender and elderly females showed the most sensitivity to the radiation-mercury exposure with low doses and to the Ligfol, according to the studied indexes.

[Smoking affects metal-ecotoxicant accumulation and genotoxic reactions in leukocytes].

The investigation was concerned with the influence of smoking on manganese (Mn), lead (Pb) and cadmium (Cd) content in the blood of metropolitan groups of varying age as well as on genotoxic reactions in leukocytes after test irradiation ex vivo. The study involved 325 inhabitants of St.Petersburg, aged 10-90 years. Venous blood was assayed for metal ecotoxicant content using standard AAS-flame method and DNA leukocyte decay following test irradiation (2Gy) ex vivo. Aging was shown to involve a sequence of consistently rising metal levels: Cd - Mn Pb. Relative accumulation of Pb was greater in males while that of Mn - in females. The rates of Cd, Mn, Pb accumulation in smokers were higher than in non-smokers. Smoking promoted genotoxic response to testing exposure which induced Cd-related disturbances of DHA repair system in males. Among smoking females, risk of adverse effects rose as a result of concurrent action of the genotoxic factor. It was also evident among female non-smokers when radiation was used in conjunction with enhanced concentrations of Mn and Cd. Hence, correlations between smoking and Cd, Mn, Pb accumulation, on the one hand, and Cd-related accumulation and enhanced genotoxic response in leukocytes, on the other, were established. It is likely that carcinogenic risk of tobacco smoking should be accounted for by both mere presence of a carcinogenic agent and its potential to promote Cd level thus inhibiting withdrawal of carcinogenic DNA adducts from the cellular genome.

[Prognosis of efficacy of organ-saving treatment of invasive bladder cancer].

It is suggested that Scr-index for radiation-induced apoptosis in leukocytes in vitro be determined prior to combined therapy of urinary bladder cancer in order to estimate its efficacy. It was identified by studying leukocytes of peripheral blood from patients in whony white blood cells DNA level decreased after exposure to 2 Gy and 3-hr incubation at 37 degrees C. Values over 1.0 predicted relatively longer relapse-free survival. Scr-index of over 1.20 pointed to an insignificant decrease in leukocyte count during therapy. When it ranged 1.00-0.75, leukocyte count fell by approximately 25%; S(cr)-index below 0.55 indicated grade III blood poisoning.

Comparative study of postradiation genotoxic changes in mammalian cells by biochemical and cytogenetic methods.

The results of studying the genotoxic effect of radiation on endometrial cells of irradiated rats using comet assay correlated with the index of spontaneous DNA degradation. Studying the genotoxic effect of in vitro irradiation (2 Gy) on human lymphocytes by means of chromosome analysis and fluorometric assay of nucleoids DNA in irradiated leukocytes also yielded similar results. Measuring of the biochemical marker holds much promise as an express method of evaluation of the genotoxic effect of radiation on mammalian somatic cells.

[The hemathological reactions in rats after partial screening from natural electromagnetic fields].

The influence of partial screening of EMF on the composition of white blood cells was studied in the experiments on rats. Two kinds of copper rings were used in these experiments: individual for each rat and common for the cage. It was shown that inside the ring the composition of blood cells was changed--in 3-5 hours the number of granulocytes increased and in 24 hours it restored to the initial level. The effect was more expressive in the experiments using individual rings. In control groups the experiment with plastic rings didn't reveal this effect. It was presumed that EMF prevented the decay of granulocytes. It leads to the increase of their guantity. It was revealed that there was a positive correlation between Ki-indexes of geomagnetic field (GMF) in 1-2 days before the experiments and the number of granulocytes in rats during 1995-2002. Ki-indexes reflect the degree of GMF disturbance. During magnetic storms the spreading of EMF in radio-frequency range changes. It was presumed that the effect of partial screening of EMF of rats and the activity of magnetic storms are similar in their influence on the composition of white blood cells of rats.

[Vilon effect on consequences of repeated radioactive and mercuric impact in small doses].

The purpose of the study was to determine the efficacy of vilon administration in rats after reiterated exposure to ecotoxicants (mercury in concentration near to maximum allowable one and gamma-radiation in small dose). In 24 hours after repeated radioactive and mercuric impact (RMI) and for 30 consecutive days the animals reported lymphopenia. At the same time the indices of DNA leucocytes content and structure did not differ from the parameters of intact animals, this could evidence the development of adaptation reactions. Vilon administration led to the normalization of the lymphocytes number by the 30th day after repeated irradiation (contrary to the radioactive- chemical control), while the number of granulocytes in the test group was higher than that in the intact control group. Study of the survival rate in rats revealed that Vilon reduced morbidity of rats in the course of 15 months after RMI.

Radiobiological effects of olipifat during radiation exposure.

Preventive injections of olipifat to rats (intramuscularly in a single dose of 250 mg/kg 24 h before gamma-exposure in a dose of 7.6 Gy) decrease animal mortality from 70 to 50%, the mean life span of dead rats remained unchanged. Injection of olipifat before exposure in a dose of 5.2 Gy did not change animal mortality in comparison with irradiated controls, but stimulated postradiation recovery of leukocyte count (mainly the granulocytic component and less so the increase in lymphocyte count). No appreciable effects of olipifat on the postradiation changes in individual fractions of blood leukocytes were observed in animals exposed in a dose of 7.6 Gy.

[Effect of selenium on reactions of elderly rats affected by low doses of radiochemical exposures]. / Vlianie selena na reaktsii pozhilykh krys pri vozdeistvii malykh doz radiatsionno-khimicheskikh faktorov.

The 18-months-old female rats received with drinking water Hg2(NO3) in concentration of 1 mkg/l in account to metal and a preparation of selenium "Neoselen" (Na2SeO2) in concentration of 1.3 ml/kg/day, respectively, during 1 month before and 1 month after single gamma-irradiations with 25 cGy doses. Are established early (through 24 h after an irradiation) cytologic and genotoxic reactions in leukocytes of blood, and also hematological, biochemical reactions and changes of the content and frame DNA of leukocytes of blood in 30 day after an irradiation? Features of action of low doses of radiation in a combination to ions of mercury and their combination with a preparation of selenium are revealed. Communication of postradiating effects--changes of indexes of DNA of leukocytes of blood with reduction of life expectancy of animals is shown. The data are received, permissive to draw the conclusion, that the preparation of selenium in utilised concentrations, essentially not influencing on lifetime at low doses of radiation--mercury affecting is capable to improve quality of life of elderly animals

[Assessment of genotoxicity and late effects of radiation and chemical exposures]. / Otsenka genotoksichnosti i otdalennykh éffektov radiatsionno-khimicheskikh vozdeistvii.

The 3-month-old female rats received with drinking water PbCl2 or Hg2(NO3)2 in concentrations 100 or 1 mkg/l in account to metal, respectively, during 1 month before and 1 month after single gamma-irradiation with 25 or 50 cGy doses. The features of action of lead- and mercury-ions revealed in combination with low doses radiation. In case of the mercury ions introduction the relationships had been shown between early postradiation biochemical effects (changes of blood leucocyte DNA indexes) and blood granulocyte changes in 1 month after irradiation, and correlation of postradiation repair results with life span shortening as well.