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BACKGROUND: The causal relationship between mutagenesis and carcinogenesis is well known. Hence the wide interest in the study of the mutagen-modifying effects of natural and synthetic compounds. Particular attention is drawn to widespread compounds. One of them, metformin, is widely used as a hypoglycemic drug. AIM: evaluation of the influence of metformin on the cytogenetic effects of doxorubicin and cyclophosphamide in mouse bone marrow cells. MATERIALS AND METHODS: Male F1 CBAxC57Bl/6 hybrid mice were used. Cyclophosphamide (20 mg/kg) or doxorubicin (10 mg/kg) was administered intraperitoneally, metformin was given orally once or for 4 consecutive days. The latter administration of metformin was combined with mutagen administration. Cytogenetic preparations of bone marrow cells were prepared 18 hours after metformin administration and 24 hours after its combined administration with mutagens. Chromosomal aberrations were analyzed according to accepted protocols. RESULTS: Metformin per se showed no cytogenetic activity at doses of 500, 1000, and 2000 mg/kg. At a dose of 500 mg/kg, but not 100 or 250 mg/kg, metformin reduced the cytogenetic effects of doxorubicin. Metformin administered once and for 4 days at doses of 100, 250, and 500 mg/kg or once at doses of 10 and 20 mg/kg increased the number of metaphases with chromosome aberrations induced by cyclophosphamide by a factor of 2 to 3. At doses of 2.5 and 5 mg/kg, metformin had no modifying effect on the mutagen effect. CONCLUSION: Metformin attenuates the cytogenetic effects of doxorubicin and enhances the cytogenetic activity of cyclophosphamide in mouse bone marrow cells. This allows us to conclude that metformin has mutagen-modifying properties.

Based on the selected criteria data from studies of the genotoxic activity of antiepileptic drugs in eukaryotic test systems in vitro and in vivo, performed by DNA comet assay, chromosomal aberrations and micronuclei assays, published in the period 19952022, were selected and summarized. Among the 20 drugs reviewed, for one drug (N03AA05 Benzobarbital), there are no data on studies of genotoxic activity; for 7 drugs information is presented only as a summary on the FDA and EMA websites without primary data and information on experimental designs. Among the remaining 12 drugs, only three drugs (phenobarbital, valproic acid and levetiracetam) have information on in vivo studies, both by DNA damage assay and by cytogenetic methods. Based on known publications, it is impossible to draw reasonable conclusions about the genotoxic potential of individual drugs. The available data are fragmentary, incomplete and contradictory. It remains to state the facts of detection of genotoxic effects in individual drugs in separate studies. In general, there is no doubt about the potential genotoxic hazard of this group the drugs in. Additional studies are needed to clarify the data on the genotoxicity of antiepileptic drugs including beyond the standard protocols. In the course of their implementation, one should take into account the possible tissue-specific manifestation of antiepileptics genotoxicity, as indicated by the facts of genotoxic effects detection in tissue cells that are not targets in classical genotoxic studies. The expediency of objectifying approaches when choosing a drug for safe therapy, taking into account information about its genotoxicity, is emphasized, and the prospects for possible studies on antigenotoxic prophylaxis in patients with epilepsy are pointed out.

According to the literature genotoxic properties of about a half of hypoglycemic drugs have not been investigated in accordance with the recommended methodology, and studies of the mutagen-modifying activity of antidiabetic drugs are sporadic. Based on the available published data, it is impossible to conclude about either presence or absence of genotoxic / antigenotoxic potential of antidiabetic drugs. There is evidence of the antimutagenic activity of metformin; in relation to other drugs, studies of mutagen-modifying activity have not been carried out or are represented only by a few articles. Further study of the genotoxic properties of hypoglycemic drugs is required in accordance with modern approaches and requirements, as well as an assessment of their mutagen-modifying activity.

The existing concepts of antimutagenesis are briefly reviewed. Published reports on antimutagenic and proapoptotic properties of some polyphenols and compounds of other chemical groups obtained in representative in vitro and in vivo experiments on eukaryotic test systems are discussed. The relationships between the antimutagenic and proapoptotic properties of the analyzed compounds (naringin, apigenin, resveratrol, curcumin, N-acetylcysteine, etc.) are considered in favor of the hypothesis on induced cell death as an antimutagenic tool.

DNA damage quantified as the comet tail length was assessed using in vitro and in vivo comet assay on one- and two-cell mouse embryos obtained by natural mating. The use of a protocol with three layers of agarose reduces the embryo loss and makes it possible to study a small number of embryos. A significantly lower level of basal, but not induced DNA damage was found in embryos with cleaved zona pellucida compared to embryos with intact zona pellucida. There were no significant differences in the length of the comet's tail between embryos lysed in different lysis solutions, both in cases of basal and induced DNA damage. A significant increase in the comet tail length was detected in one-cell embryos of mice treated with methyl methanesulfonate and etoposide compared to the control. The data show that DNA damage induced in maternal germ cells persists, which can be detected in embryos using the comet assay.

Inter- and intralaboratory variability of results is still a serious issue in the comet assay. There are several technical conditions of procedure, which may critically affect the results and electrophoresis terms were identified as main. A comparative assessment of the expected and actual electric field strength in five electrophoretic tanks and the contribution of the revealed differences to the variability in DNA damage carried out. Only for one tank, the measured electric field strength coincided with the expected 1 V/cm, while for four it ranged from 0.6 to 2.0 V/cm. The values of DNA damage assessed in the same samples of mouse kidney cells differed between tanks up to 4.7-fold for induced and up to 10-fold for spontaneous DNA damage. High local variations in the electric field strength and solution temperature across the platform as well as in %DNA in the tail of identical cell samples within electrophoresis runs also revealed. These variations were reduced by recirculation of electrophoresis solution. The results show that discrepancy between the estimated and the actual electric field strength can be reason of inter-laboratory variation of the comet assay results. Recirculation of the solution during electrophoresis will be useful to control of intra-laboratory and intra-assay variations.

The study investigated antigenotoxic and antimutagenic activity of novel lignin-derived polyphenolic composition (BP-C2) with ammonium molybdate towards cyclophosphamide and dioxidine in the bone marrow, blood and liver cells of BALB/c mice. BP-C2 was given to mice via gavage at 60, 80 and 120 mg/kg once 1 h before single intraperitoneal injection of a genotoxic agent. 1.5 h and 3 h after dioxidine or cyclophosphamide injection, respectively, cellular suspensions were obtained from mice and assessed with the comet test and cytogenetic analysis of bone marrow cells. It was observed that antigenotoxic activity of BP-C2 against DNA damage induced by dioxidine, a prooxidant genotoxic agent, in the bone marrow, liver and blood cells of mice in vivo was more pronounced at 60 and 80 mg/kg than at 120 mg/kg. When cyclophosphamide was used to induce a DNA damage, the genoprotective effect of BP-C2 was observed in bone marrow, liver and blood cells at 60 mg/kg dose but the effect was not significant at 80 mg/kg. When co-administered with 120 mg/kg BP-C2, cyclophosphamide induced a higher level of DNA damage in liver cells, but its genotoxic effect in bone marrow and blood cells was the same as when it was administered alone. When assessing the effect of BP-C2 on chromosomal aberrations induced by cyclophosphamide and dioxidine in bone marrow cells, it was revealed that all three tested doses of BP-C2 significantly decreased the number of cells with chromosome abnormalities. Thus, BP-C2 has a pronounced antimutagenic and genoprotective effects.

In experiments on BALB/c mice, prediabetes was modeled by administration of streptozotocin in a dose of 130 mg/kg. DNA damage was assessed by the method of DNA comets. Noopept (0.5 mg/kg intraperitoneally) was administered for 14 days before and for 6, 13, or 14 days after streptozotocin administration. Despite moderate hyperglycemia and increased malondialdehyde level, the intensity of DNA damage in cells of the pancreas, liver, and kidneys significantly surpassed the control values. Noopept normalized these parameters due to its pronounced antigenotoxic effect. For both the damaging effect of streptozotocin and the normalizing effect of Noopept, DNA changes manifested mainly in terms of atypical DNA comets. Our findings confirm the role of DNA damage in the pathogenesis of diabetes. They indicate the possibility of pharmacological protection of pancreatic β cells with the neuroprotective drug and provide an important argument in favor of the hypothesis about the similarity of the mechanisms of formation of the resistance of neurons and β cells to the cytotoxic influences.

Antiviral drug Kagocel in concentrations of 0.0008, 0.004, 0.02, 0.1, 0.5, and 2.5 mg/ml with or without metabolic activation does not induce gene mutations in S. typhimurium strains ТА98, ТА100, ТА1535, and ТА1537 and in a combination of E. coli strains pKM101 and uvrA. A single intragastric administration of Kagocel in a daily therapeutic dose and a 10-fold daily therapeutic dose to male mice or multiple administrations in daily therapeutic dose to male and female mice did not led to a significant increase in the percentage of chromosomal aberrations in the bone marrow cells. DNA comet assay revealed no significant increase in the incidence of DNA breaks in cells of mouse testes after single or multiple administration of Kagocel at daily therapeutic and 10-fold daily therapeutic doses. Our results indicate that Kagocel exhibits no genotoxic activity in the studied dose range.

The existing concepts of antimutagenesis are briefly reviewed. Published reports on antimutagenic and proapoptotic properties of some polyphenols and compounds of other chemical groups obtained in representative in vitro and in vivo experiments on eukaryotic test systems are discussed. The relationships between the antimutagenic and proapoptotic properties of the analyzed compounds (naringin, apigenin, resveratrol, curcumin, N-acetylcysteine, etc.) are considered in favor of the hypothesis on induced cell death as an antimutagenic tool.

It is shown in the experiments on rats that prenatal exposure to peat smoke for 44 min daily during days 1 to 13 of gestation leads to a 4–5-fold increase in the DNA damage (the DNA-comet alkaline assay) in the placenta and embryos. The animals receiving afobazole in doses of 1 and 10 mg/kg per os showed a significant 53–60% decrease in the genotoxic effects of peat smoke. Interindividual and intraindividual differences in genotoxic and antigenotoxic effects are observed. In some cases, afobazole reduces the DNA damage to the control level

The phenomenon of atypical DNA comets observed in experiments using DNA-comet assay is described and illustrated. The current hypotheses explaining the nature of atypical DNA comets and our own take on the issue are considered. The practical importance of the registration of atypical DNA comets during the assessment of genotoxicity is discussed.

The class of carbazoles includes compounds with high biological activities and broad spectra of action. PLX01107 and PLX01008 are xenomycins, a new subclass of antimicrobial carbazole derivatives demonstrating strong antifungal activity in vitro. We performed three tests, a bacterial reverse mutation assay (Ames test), in vitro cytokinesis-block micronucleus assay, and chromosome aberration test in mouse bone marrow cells, to investigate the possible genotoxicity of these compounds. Despite their structural similarity, the two compounds had different genotoxicity profiles. PLX01008 showed positive effects in all assays. PLX01107 showed no mutagenicity in the Ames test but demonstrated strong cytogenetic activity in vitro and in vivo. PLX01107 was also tested in the in vivo alkaline comet assay, where a weak but statistically significant increase in DNA damage was seen in liver cells 24h after treatment. Significantly increased levels of formamidopyrimidine DNA glycosylase (FPG)-sensitive sites were found in bone marrow cells of PLX01107-treated mice (FPG-modified comet assay), suggesting induction of oxidative or alkylation damage to DNA.

The genotoxicity of cationic lipopeptide nanoparticles (cLPNPs) was evaluated in vivo and in vitro comet assay and the in vivo chromosome aberrations test. In vitro comet assay, human blood cells were exposed to cLPNPs at the concentration of 2.5, 5, 10, 20, 40 and 100 μg/mL. Significant DNA damage was observed after 1 h exposure, but no effects were detected after 3 h. In vivo, cLPNPs were administered in single or five daily injection doses at 8, 20 and 40 mg/kg of body weight by subcutaneous injection to male mice. The cLPNPs caused DNA damage in the liver, lung and kidney, but not in the spleen. The kidney was more prone to genotoxic effects that persisted from 24 h to 14d after a single injection of cLPNPs. No statistically significant increase in the percentage of cells with chromosomal aberrations above the vehicle control was observed in mice bone marrow after a single or repeated injection of cLPNPs. In summary, cLPNPs shown to be genotoxic both in vivo and in vitro. The results suggest the importance of the use of highly sensitive methods, such as the comet assay, in order to determine the full genotoxic potential of nanoparticles.

Background. It was shown that prenatal exposure to peat smoke leads to disturbances of fetal and postnatal development in rats. Genotoxic mechanisms may be involved to these deleterious effects. The objective of the present study was to evaluate the DNA damage and its modification by known antimutagen afobazole in placenta and embryo of rats, exposed to peat smoke. Materials and methods. Pregnant rats were exposed to filtered air (control), to peat smoke or to peat smoke with receiving of afobazole (1 or 10 mg/kg, per os) for 44 min, daily during days 1 to 13 of gestation. At the day 13 four placenta and embryo samples from each rat were obtained for DNA damage analysis using the alkaline comet assay. Results. A significant, 4-5 folds increase in the DNA damage values (% DNA in tail) was found in placenta and embryos of rats exposed to peat smoke. Genotoxic effects were generally more pronounced in placenta. Exposure to peat smoke together with receiving of afobazole at the doses 1 and 10 mg/kg showed a significant, 53-60 % decrease in the mean % DNA in tail values in both placenta and embryos. Clear inter and intra-individual differences in genotoxic as well as in antigenotoxic effects were observed. For the some placenta or embryo samples were seen reducing of DNA damage to the control level. Conclusion. Exposure of pregnant rats to peat smoke causes DNA damage in placenta and embryos. This smoke-induced genotoxicity might be decreased or prevented by antimutagenic agents.

Usnic acid, which is the most widespread and well-studied secondary lichen compound, has antibacterial and cytotoxic effects. Usnic acid is present in lichens as the (+)- and (-)-enantiomers, which have different biological activities. We used a DNA-comet assay to determine the genotoxic effect of (+)- and (-)-usnic acid in the liver and kidney cells of mice. The genotoxic effect of usnic acid was only observed 1 h after oral administration. Usnic acid doses of 100 and 50 mg/kg resulted in DNA damage in the liver and kidney cells. The genotoxic effect of usnic acid is associated with oxidative stress in cells. There were no significant differences in the effects of (+)- and (-)-enantiomers.

The phenomenon of atypical DNA comets in experiments using DNA comet assay is described and illustrated. The current hypotheses explaining the nature of atypical DNA comets and own vision of the issue are considered. The practical importance of the registration of atypical DNA comets in assessing the genotoxicity is discussed.

The effect of usnic acid enantiomers on the genotoxic effects of dioxidine and methyl methanesulfonate was studied in vitro in human peripheral blood lymphocytes by the DNA comet method. We found that usnic acid enantiomers in a concentration range of 0.01-1.00 μM demonstrated pronounced antigenotoxic activity and reduced DNA damage induced by genotoxicants by 37-70%. In the same concentration range, the test enantiomers reduced the level of atypical DNA comets (hedgehogs) induced by genotoxicants by 23-61%. The test compounds did not modulate the effects of genotoxicants in a concentration of 10 μM and potentiated them in a concentration of 100 μM. The modifying activity of usnic acid did not depend on spatial configuration and on the used model genotoxicant.

We performed an inter-laboratory study to determine the variation of comet assay results and to identify its possible reasons. An exchange of slides between Labs in different stages of the comet assay protocol was performed. Because identical slides, durations of alkali treatment and electrophoresis, and similar electric field strengths (2.0 V/cm and 2.14 V/cm) were used, we concluded that the observed inter-laboratory difference in the results is directly associated with the electrophoresis step. In Lab 1, mouse bone marrow cells were exposed to methyl methanesulfonate at concentrations of 10, 25 and 50 μM for 3 h at 37 °C. In Lab 2, cells the same as in Lab 1 were immobilized in LMA on slides and exposed to X-rays at doses of 3-8 Gy. We found that the transportation of slides after lysis or electrophoresis step, as well as different dyes used for scoring did not produce any significant effect on the results. No substantial difference in the data was also revealed when various software packages were used for image analysis. The temperature of the alkaline solution was shown to increase during electrophoresis and, besides, the temperature heterogeneity of the solution took place in the area of the platform, with a maximum in the middle of the chamber. The temperature heterogeneity could affect the rate of conversion of alkali labile sites into single stranded breaks. Thus, it was clearly indicated that real temperature variations during the alkali treatment and electrophoresis were an essential factor in the variability of the results between our Labs.

The chromosome aberration test in bone-marrow cells of mice was used to study the influence of valocordin on spontaneous and induced clastogenesis. Valocordin showed no inherent clastogenic activity. In experiments with pretreatment and with single or repeated combined administration valocordin in doses of 0.03, 0.3, and 3 mL/kg significantly (by 47–133%) enhanced the clastogenic activity of cyclophosphamide. There was no effect of valocordin on the cytogenetic activity of dioxidine, a mutagen with a pro-oxidative mode of action. Possible mechanisms of the comutagenic activity of valocordin are discussed.

The influence of N-acetylcysteine (ACC) on the cytogenetic effects of etoposide in F1 CBA x C57BL/6 mice was studied. Etoposide introduced intraperitoneally in doses of 10, 20, 40, and 60 mg/kg has a dose-dependent clastogenic activity and has an aneugenic effect with the induction of mainly hypohaploid oocytes. ACC significantly decreases the aneugenic and clastogenic activity of etoposide (20 mg/kg) in oocytes of 6-, 9-, and 12-week-old mice during triple introduction at a dose 200 mg/kg per os. The most pronounced anticlastogenic ACC activity (an 80% decrease) was registered in 9-week-old females; a 100% decrease in aneugenesis was detected in 6-week-old female mice.

The chromosome aberration test in bone marrow cells of mice was used to study the influence of valocordin on spontaneous and induced clastogenesis. Valocordin showed no inherent clastogenic activity. In experiments with pretreatment and with single or repeated combined administration , valocordin in doses of 0.03, 0.3 and 3 ml/kg significantly (47–133 %) enhanced the clastogenic activity of cyclophosphamide. There was no effect of valocordin on the cytogenetic activity of dioxidine, a mutagen with a pro-oxidative mode of action. Possible mechanisms of comutagenic activity of valocordin are discussed.

Silicon crystal 2-5 nm nanoparticles in the form of 1-5-μ granules in water suspension were injected intraperitoneally in a single dose to male F(1)(CBA×C57Bl/6) mice or to outbred albino rats on days 1, 7, and 14 of gestation. Silicon crystal nanoparticles in doses of 5, 25, and 50 mg/kg exhibited no cytogenetic activity in mouse bone marrow cells after 24-h exposure and in doses of 5 and 25 mg/kg after 7 and 14-day exposure. A 24-h exposure to silicon nanoparticles in a dose of 5 mg/kg significantly increased DNA damage (detected by DNA comet assay) in bone marrow cells. In a dose of 50 mg/kg they considerably increased DNA damage in bone marrow and brain cells after exposure of the same duration. Silicon nanoparticles in doses of 5 and 50 mg/kg caused no genotoxic effects in the same cells after 3-h and in a dose of 5 mg/kg after 7-day exposure. Silicon crystal nanoparticles in a dose of 50 mg/kg caused death of 60-80% mice after exposure24 h. Injected in a dose of 50 mg/kg on days 1, 7, and 14 of gestation, silicon crystal nanoparticles reduced body weight gain in pregnant rats and newborn rats at different stages of the experiment, but had no effect on other parameters of physical development of rat progeny and caused no teratogenic effects.

Purpose: To determine the DNA strand breaks, oxidative DNA damage and cell death in blood and plasma total antioxidant status (TAOS) in 22 patients with severe multiple trauma. Materials and methods: The DNA comet assay was used to measure DNA strand breakage, 8-oxoguanine levels and apoptotic and necrotic nuclei in after admission (day 0) and on days 3, 5, 7 and 15. TAOS was determined by colorimetric method. Results: Trauma patients had high DNA damage at admission (p < 0.01), that further increased with maximum value on day 5 (p < 0.001). On day 15 the degree of DNA damage remained significantly elevated (p < 0.01). No significant difference in the 8-oxoguanine levels at all days examined was found. Patients had a high percentage of apoptotic and necrotic comets at admission, with maximum values on days 3 and 5. A significantly lower TAOS was observed in patients on admission and days 3, 5, 7 and 15 (p < 0.001 in all cases). A decreasing of TAOS on days 7 and 15 compared to that on admission (p < 0.05) was observed. Conclusions: Blood cells from severe trauma patients’ display increased DNA damage associated with apoptosis and necrosis. Reduced plasma TAOS and a tendency to increase of 8-oxoguanine in DNA was observed.

The cytogenetic and mutagen-modifying activity of caffeine was studied with the method of chromosomal aberrations in bone marrow cells of mice hybrids F1 CBAxC57BL/6. Caffeine per se was administered intragastrically or intraperitoneally, and in combination with mutagens--intragastrically. Mutagens injected intraperitoneally. Caffeine at doses of 10 and 100 mg/kg (single dose) and 10 mg/kg (five days) in parenteral administration and oral introduction failed to possess cytogenetic activity. In combination with mutagens caffeine (1, 10 and 100 mg/kg) had no effect on the cytogenetic activity of dioxydine (200 mg/kg/intraperitoneally) for a single coadministration, five-day pre or five-day coadministration. In combination with other mutagens under the same processing conditions caffeine at doses of 10 and 100 mg/kg significantly increased cytogenetic effects of cyclophosphamide (20 mg/kg) in the pretreatment of the animals and at the dose of 100 mg/kg significantly attenuated the cytogenetic effect of cisplatin (5 mg/kg) in single and repeated co-administration. Thus we have shown the absence of caffeine cytogenetic activity in vivo and showed the multidirectional effect of caffeine in doses far exceeding its daily consumption, to the manifestation ofcytogenetic effects of certain chemical mutagens in some modes of processing animals.

Spontaneous and in vitro induced (with 0.01 and 0.1 mg/ml dioxidine and 0.1 and 1.0 U/ml bleomycin) chromosome aberrations were counted in cultured peripheral blood cells from 11 donors before and after 2-week therapy with a vitamin complex. The complex contained the major vitamins in doses not surpassing the recommended daily doses. Vitamins had no effect on spontaneous mutations, but increased cell resistance to clastogenic effects of dioxidine in a concentration of 0.1, but not 0.01 mg/ml. Cell sensitivity to bleomycin notably increased after vitamin therapy in some donors and decreased in others, the mean parameters in the group remained virtually unchanged.

We carried out a comparative analysis of DNA damage (percentage of DNA in comet tail) and frequencies of comets in apoptotic cells in BM samples and cultures of BM multipotent mesenchymal stromal cells at different terms of culturing (passages 3-11). The levels of DNA damage in mesenchymal stromal cells remained unchanged during culturing (3.5 ± 0.9 and 4.4 ± 1.2%) and did not differ from those in BM cells (3.6 ± 0.8%). In BM samples, 10-28% atypical cells with high level of DNA damage were detected. In mesenchymal stromal cells, 2.8 ± 0.9 and 3.6 ± 1.8% apoptotic cells were detected at early and late passages, respectively.

The DNA comet assay was used to evaluate the severity of genotoxic changes in embryonic tissues and placenta of rats daily exposed to tobacco smoke per se or in combination with an anxiolytic agent afobazole. The exposure to tobacco smoke (4 cigarettes containing 13 mg tar and 1 mg nicotine per 72 dm(3)) for 20 min on days 1-13 of pregnancy increased the degree of DNA damage and elevation of apoptotic DNA comets in cells of the placenta and embryo from pregnant rats. Afobazole (1 and 10 mg/kg orally) reduced the genotoxic effect of tobacco smoke and decreased the amount of apoptotic DNA comets in placental tissue and embryonic tissue from rats.

We developed an original method of isolation and analysis of cytogenetic micropreparations of mouse oocytes including treatment with buffered hypotonic saline, paraformaldehyde fixation, and fluorescent staining. The method had several advantages, including high quality of sections and low labour intensity.

Using comet assay we studied the effect of anxiolytic afobazole, exhibiting also antioxidant and antimutagenic properties, on spontaneous and ex-vivo hydrogen peroxide-induced DNA damage in blood cells from patients with systemic lupus erythematosus. Afobazole treatment (30-60 mg/day for 1 month) in addition to standard therapy decreased spontaneous level of DNA damage in blood cells. The level of ex vivo hydrogen peroxide-induced DNA damage decreased by 49% in this group of patients. The number of cells hypersensitive to hydrogen peroxide yielding DNA comets with highly damaged DNA also decreased by 51%. No significant changes in the analyzed parameters were found in the placebo group. Addition of afobazole to complex therapy of patients with systemic lupus erythematosus reduced the level of DNA damage in blood cells and improved cell resistance to oxidative genotoxic exposure.

The influence of a new 2-mercaptobenzimidazole derivative afobazole on cytogenetic effects of dioxidine and cyclophosphamide was studied by counting chromosome aberrations in bone marrow cells of C57B1/6 mice. Afobazole (1–100 mg/kg perorally) exhibited antimutagenic activity determined by its antioxidant properties. This activity depended on the dose and treatment shedule.

There are presented the results of genotoxicologic, immunologic and allergologic examinations which were conducted within the framework of integrated medical and biological assessment of genetically modified rootworm Diabrotica spp.-protected maize event MIR604. Analysis of damages of DNA and structural chromosome aberrations, assessment of the allergenic potential and immunoreactive properties has not confirmed any genotoxic, allergenic and immunotoxic effect of maize event MIR604.

Experiments of mice and rats showed the ability of afobazole (1, 10, and 100 mg/kg, p.o.) upon single, 5-day combined, and 5-day preliminary administration to prevent or significantly decrease the clastogenic effects of the prooxidant agent dioxidine (100 and 300 mg/kg, i.p.) and the clastogenic and teratogenic effects of the alkylating agent cyclophosphamide (20 mg/kg, i.p.).

There are presented the results of genotoxicologic, immunologic and allergologic examinations which were conducted within the framework of integrated medical and biological assessment of genetically modified rootworm Diabrotica spp.--protected and glyphosate tolerant maize event MON 88017. Analysis of damages of DNA and structural chromosome aberrations, assessment of the allergenic potential and immunoreactive properties has not confirmed any genotoxic, allergenic and immunotoxic effect of maize event MON 88017.

Genotoxic properties of dihydroquercetin were in vivo studied by the method of chromosome aberrations counting and DNA-comet assay. Dihydroquercetin administered repeatedly (5 times, 0.15 and 1.5 mg/kg) or once in doses of 15, 150, and 2000 mg/kg induced no DNA damages in mouse bone marrow, blood, liver, and rectal cells. Single administration of this preparation in doses of 1.5 and 150 mg/kg and 5-fold administration in a dose of 1.5 mg/kg had no effect on the level of chromosome aberrations in mouse bone marrow cells.

Peripheral blood leucocytes of healthy donors, both intact and mutagen-processed with cadmium chloride, dioxidine, and bleomycin in vitro, were studied with cytogenetic methods in G2 cell cycle period before, during, and after 14- and 30-day oral administration of vitamin and vitamin-mineral complexes. The study found that intake of complexes containing vitamins in total doses exceeding day requirements did not increase the rate of spontaneous mutations and decreased the sensitivity of human cells to the cytogenetic activity of chemical mutagens. At the same time, vitamin complexes of certain quantitative and qualitative composition were shown to be capable of giving rise to comutagenic modification of sensitive cells to the action of separate mutagens in certain concentrations in vitro. The above effects of anti- and comutagenic modification depend on the duration of intake, the quantitative and qualitative composition of the vitamin complex, the nature of mutagens, and the level of induced cytogenetic lesions.

Using the method of semiquantitative reverse transcription PCR we studied the expression of hOGG1 gene (exons 1-4 and 1-7) in peripheral blood cells from patients with systemic lupus erythematosus. Expression of this gene was disturbed in 9 of 18 patients (50%). In two patients mRNA of this gene was not expressed. In 5 patients hOGG1 mRNA was practically absent and was detected only after 35 amplification cycles. Suppression of exons 4-7 expression was detected in two of these cases and expression of both mRNA fragments (exons 1-4 and 4-7) was suppressed in 3 cases. In two patients a decrease in the relative content of exons 4-7 mRNA was found against the background of normal level of mRNA for exons 1-4. In none of the patients changes in the sequence of hOGG1 mRNA exons were revealed by parallel DGGE analysis. Our findings attest to disturbances in the expression of hOGG1 gene, primarily alpha-hOGG1 isoforms of the enzyme, in peripheral blood cells in patients with systemic lupus erythematosus.

Study was performed by counting cells with chromosomal aberrations in C57Bl/6 mice. Bark dry extract was given perorally in doses of 50, 150, 450, and 1500 mg/kg. Mutagens dioxidine and cyclophosphamide were injected intraperitoneally in doses of 200 and 20 mg/kg, respectively. Bark dry extract in doses of 150 and 1500 mg/kg did not possess cytogenetic activity. Bark dry extract in doses of 50, 150, and 450 mg/kg significantly decreased the cytogenetic effect of mutagens under various regimens of treatment with the preparation (single combined administration, 5-day pretreatment, and 5-day combined administration). Our results indicate that bark dry extract possesses antimutagenic properties.

The total antioxidant capacity (TEAC assay) of blood plasma from healthy donors was studied before and after 2- and 4-week consumption of the vitamin and mineral complex containing the major antioxidant vitamins and cofactors of antioxidant enzymes. Before the treatment the donors were divided into 2 subgroups with initially high and low total antioxidant capacity. After 2-week course of vitamin and mineral complex the total antioxidant capacity considerably decreased in group 1 donors, but increased in group 2 donors. After 4-week course this index increased in donors of both subgroups and slightly surpassed the baseline level typical of individuals with high total antioxidant capacity.

Spontaneous and in vitro induced (with 0.01 and 0.1 mg/ml dioxidine and 0.1 and 1.0 U/ml bleomycin) chromosome aberrations were counted in cultured peripheral blood cells from 11 donors before and after 2-week therapy with a vitamin complex. The complex contained the major vitamins in doses not surpassing the recommended daily doses. Vitamins had no effect on spontaneous mutations, but increased cell resistance to clastogenic effects of dioxidine in a concentration of 0.1, but not 0.01 mg/ml. Cell sensitivity to bleomycin notably increased after vitamin therapy in some donors and decreased in others, the mean parameters in the group remained virtually unchanged.