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V N Anisimov

Publications and source records attributed to V N Anisimov.

At least 19 recordsLinked to original sources
PubMed1999

Prevention of spontaneous and chemically induced carcinogenesis using activated carbon fiber adsorbent. II. Inhibitory effect of the activated carbon fiber adsorbent 'Aqualen' on N-methyl-N'-nitro-N-nitrosoguanidine-induced gastric carcinogenesis in rats.

Two-month-old female LIO rats were given N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) with tap water in a concentration of 100 mg/l for 12 months (groups 1 and 2) or were kept without the carcinogen treatment (groups 3 and 4). From the first day of exposure to MNNG rats from groups 2 and 3 were given activated carbon fiber adsorbent Aqualen in their diet five times per week together with lab chow in a daily dose of 100 mg/kg of body weight. The experiment was finalized 16 months after first exposure to the carcinogen. The total stomach adenocarcinoma incidence was 43% in group 1 and 39% in group 2, whereas invasive stomach adenocarcinomas occurred in 36% and 8% of rats from groups 1 and 2, respectively (P < 0.05). Tumors other then stomach sites (duodenum and liver) only developed in rats from group 1 (29%). No lesions were observed in rats exposed to Aqualen without MNNG. Thus, our results demonstrate the inhibitory effect of the activated carbon fiber adsorbent Aqualen on stomach carcinogenesis in rats.

Adsorption↗
PubMed1999

Prevention of spontaneous and chemically induced carcinogenesis using activated carbon fiber adsorbent. III. Inhibitory effect of the activated carbon fiber adsorbent 'Aqualen' on 1,2-dimethylhydrazine-induced intestinal carcinogenesis in rats.

Two-month-old outbred female LIO rats were exposed weekly to 15 (experiment I, groups 1, 2 and 3) or to 5 (experiment II, groups 4, 5 and 6) subcutaneous injections of 1,2-dimethylhydrazine (DMH) at a single dose of 21 mg/kg of body weight. From the day of the first injection of the carcinogen, the rats from groups 2, 3, 5 and 6 were given Aqualen in their diet. In both experiments rats were fed Aqualen five times per week together with lab chow at the daily dose of 0.1 g/kg (groups 2 and 5) or 1.0 g/kg (groups 3 and 6) of body weight. Additionally, other rats were not exposed to the carcinogen and served as an intact control (group 7) or were given Aqualen with the diet at the daily dose of 0.1 g/kg (group 8) or 1.0 g/kg (group 9). These experiments were finalized 6 months after the first injection of DMH. In experiments I and II, the majority of tumors were localized in the descending colon. Tumors of the small intestines developed only in rats from experiment I. The total incidence of colon tumors as well as tumors in different parts of the colon and the mean number of tumors per rat were much higher in rats from all groups in experiment I than in the rats from experiment II. In experiment I supplementation of Aqualen to the diet was followed by a decrease in the incidence of tumors in the ascending colon and by a decrease in the number of tumors per rat in both ascending and descending colons regardless of the dose of the enterosorbent. In experiment II the effect of Aqualen was stronger than in experiment I -- the enterosorbent decreased both the tumor incidence and the multiplicity in the total colon, its ascending and descending parts and in the rectum. In experiments I and II the percentage of small colon tumors among rats exposed to Aqualen (groups 2, 3, 5 and 6) was higher than that of the controls (groups 1 and 4). Most of detected intestinal tumors were classified as adenocarcinomas. The level of tumor differentiation was higher in rats exposed to Aqualen. There were no pathological changes observed in rats exposed to Aqualen without DMH. Carcinogen treatment resulted in an increase of serum glucose and cholesterol levels whereas Aqualen normalized these changes. Thus, our results demonstrate the inhibitory effect of activated carbon fiber adsorbent Aqualen on intestinal carcinogenesis in rats.

1,2-Dimethylhydrazine↗
PubMed1999

Effects of melatonin on N-nitroso-N-methylurea-induced carcinogenesis in rats and mutagenesis in vitro (Ames test and COMET assay).

The effect of melatonin, an indole hormone of the pineal gland, on the initiation of N-nitroso-N-methylurea (NMU)-induced carcinogenesis in rats and mutagenesis in vitro has been investigated. Two-month-old female LIO rats (groups 1 and 2) were exposed to a single injection of NMU (50 mg/kg of body weight, i.v.). Rats from group 2 were given melatonin orally (20 mg/l) from 18:00 to 09:00 h over 3 days (2 days before and 1 day after NMU injection). Animals from group 1 (control) were administered the solvent (ethanol/water, 1:1000). Rats were followed up to natural death or were sacrificed when moribund. Tumors developed both in rats treated with NMU alone (50.0%) and in rats exposed to NMU plus melatonin (34.8%). The percentage of malignant tumor-bearing rats in group 2 (21.7%) was lower (P < 0.02) than that in the other group (41.7%). Melatonin also decreased the multiplicity of malignant tumors 1.3-fold and reduced the incidence of malignancies in some organs. Two in vitro tests were used for mutagenesis studies: the Ames test (strains TA 100 and TA 102 of Salmonella typhimurium) and the Single Cell Gel Electrophoresis assay (SCGE assay or COMET assay) performed on CHOK1 cells. Melatonin itself revealed no genotoxic effect in either of the tests. No protective action of melatonin (at doses of up to 2 micromol/plate) towards NMU was found in the Ames test. In contrast, in the SCGE assay a slight, but statistically significant (P < 0.001), dose-related anticlastogenic effect of melatonin (10(-10)-10(-7) M) was observed. Thus, our data indicate that melatonin may act as an anti-initiating hormone in NMU-induced carcinogenesis and possess anticlastogenic activity towards NMU in CHOK1 cells.

Animals↗
PubMed1999

Melatonin and colon carcinogenesis. II. Intestinal melatonin-containing cells and serum melatonin level in rats with 1,2-dimethylhydrazine-induced colon tumors.

Two-month-old outbred female LIO rats were injected weekly with a single dose of 1,2-dimethylhydrazine (DMH; 21 mg/kg of body weight) administered s.c. for 15 consecutive weeks. From the day of the 1st injection of the carcinogen the part of rats were given five days a week during the night time (from 18.00 h to 08.00 h) melatonin dissolved in tap water, 20 mg/l. The experiment was terminated in 6 months after the first injection of the carcinogen. The concentration of melatonin in the serum was estimated by radioimmunoassay in rats exposed to DMH alone or in intact control rats in the morning (between 10.00 and 11.00 hours) and night (between 24.00 and 01.00 hours) time. Number of melatonin-containing cells (M-cells) and their optical density were estimated by immunohistology in normal mucosa of glandular stomach, duodenum, ileum and descending colon of tumor-bearing animals from groups exposed to DMH or DMH+melatonin. It was shown that serum melatonin levels in rats with colon tumors was increased as compared with controls. However there was no diurnal rhythm of serum melatonin of colon tumor-bearing animals as compared to intact controls. The number of M-cells was decreased in all tissues studied in rats with DMH-induced colon tumors in comparison to corresponding controls: by 2.0 times in stomach, by 1.8 time in duodenum, by 1.3 times in ileum, and by 1.8 times in colon. In ileum and colon of rats treated with DMH+melatonin the number of M-cells was similar to control level whereas in stomach and duodenum this number was significantly higher than that in rats treated with DMH alone, but less than in corresponding controls. Relative content of melatonin in enterochromaffin cells of all parts of gastrointestinal tract evaluated as optical density of the cells and was decreased in rats exposed with DMH alone in comparison to the controls and was normalized and similar to the norm level in rats treated with DMH+melatonin. Thus, exogenous melatonin prevent a decrease in numbers of melatonin-containing cells as was observed in gastrointestinal tract (GIT) of rats exposed to DMH. This preventive action of melatonin correlated well with its anticarcinogenic effect.

1,2-Dimethylhydrazine↗
PubMed1998

Modulatory effects of melatonin on genotoxic response of reference mutagens in the Ames test and the comet assay.

The effect of a potent endogenous antioxidant, the pineal gland indole melatonin (MLT) on the mutagenicity of twelve well-known mutagens and carcinogens has been investigated using two in vitro tests the Ames test and the single cell gel electrophoresis assay (SCGE assay or COMET assay). The 12 mutagens used were 7, 12-dimethylbenz(a)anthracene (DMBA), benzo(a)pyrene (BP), 2-aminofluorene (AF), 1,2-dimethylhydrazine (DMH), bleomycin, cyclophosphamide (CP), 4-nitroquinoline-N-oxide (NQO), 2,4, 7-trinitro-9-fluorenone (TNF), 9-aminoacridine (AA), N-nitrosomethylurea (NMU), mitomycin C and sodium azide tested in the absence or in the presence of S9 mix. MLT alone turned out neither toxic nor mutagenic in the Ames test and revealed clastogenic activity at the highest concentration tested (100 microM) in the SCGE assay. In four Salmonella typhimurium tester strains TA 97, TA 98, TA 100 and TA 102 MLT significantly reduced the mutagenicity of chemicals which require S9 activation. In the SCGE assay performed on CHO cells, preincubation with MLT led to a strong inhibition of clastogenic activities of DMBA and CP, and in a lesser extent with BP and NMU. With mitomycin C, MLT exacerbated responses in both tests. The possible mechanisms of MLT's inhibitory action are discussed.

Animals↗
PubMed1998

Pineal peptide preparation epithalamin increases the lifespan of fruit flies, mice and rats.

Treatment with pineal peptide preparation epithalamin was followed by the increase of the mean lifespan of female D. melanogaster, SHR mice, C3H/Sn mice and LIO rats by 11-31% (P < 0.05). Ninety percent mortality as well as maximum lifespan were increased in fruit flies, C3H/Sn mice and rats. Mortality rate was decreased by 52% in D. melanogaster, by 52% in rats, by 27% in C3H/Sn mice. It did not change in SHR mice exposed to epithalamin. Treatment with the pineal peptide increased MRDT in flies, C3H/Sn mice and rats. It has been shown that epithalamin increased synthesis and secretion of melatonin in rats and inhibits free radical processes in rats and in D. melanogaster. It is suggested that antioxidative properties of epithalamin lead to increased lifespan of three different animal species.

Animals↗
PubMed1998

Prevention of spontaneous and chemically-induced carcinogenesis using activated carbon fiber adsorbent. I. Effect of the activated carbon fiber adsorbent 'Aqualen' on spontaneous carcinogenesis and life-span in mice.

Female SHR mice were fed the activated carbon fiber adsorbent Aqualen beginning at the age of 3 months through their life. Mice were fed Aqualen five times per week together with lab chow at a daily dose of 100 mg/kg b.w. The addition of Aqualen into food did not significantly influence the dynamics of body weight and the mean life-span of the animals. At the same time, the age at 90% mortality of mice was 4 months longer in the group exposed to Aqualen. There were no statistically significant differences in the incidence of all tumors and malignant tumors in the group of mice treated with Aqualen as compared with the control group. However, in the group of mice exposed to Aqualen, there was a 1.4 times reduction of the mean number of tumors per mouse. Feeding mice with the adsorbent led to a 4 months longer life-span in animals with any tumors and to a 5 months longer life-span in animals bearing malignant tumors (P < 0.05). No carcinogenic effect of Aqualen was found. It could be supposed that Aqualen has some geroprotective and anticarcinogenic properties.

Adsorption↗
PubMed1998

[Effect of computer terminal irradiation on mice prior to mating on tumorigenesis in the offspring].

Male and female SHR mice were exposed to irradiation from the display terminal of a personal computer, 1 hr, 5 times a week for 2 weeks. Then the animals were mated and tumor yield in the progeny was studied. The descendants of intact mice were used as control. A significant increase in total tumor incidence was recorded in males and females in the experimental group. Adenocarcinoma of the mammary gland highly featured in females while lung tumors--in males.

Adenocarcinoma↗
PubMed1998

[Effect of the enterosorbent Aqualen on intestinal carcinogenesis induced by 1,2-dimethylhydrazine in rats].

Subcutaneous injections of 21 mg/kg 1,2-dimethylhydrazine were given weekly to 134 female LI0 rats. In the first series, 73 rats received 15 injections while 63 animals--5 injections (series 11). Some rats were also fed Aqualen (0.1 or 1.0 g/kg b.w.) during the whole experiment (6 months). In run 1, all animals developed malignant tumors of the colon. However, multiple tumors in Aqualen-fed rats were significantly less frequent than in those receiving carcinogenic agent alone. Also, Aqualen appeared to inhibit the development of carcinoma in the small intestine. In run 11, Aqualen treatment was followed by decreased incidence and multiplicity of tumors both in the entire large intestine and ascending and descending colon. Rectal tumor incidence was lower, too. In both runs, tumor size in enterosorbent-fed animals was smaller than in controls. All intestinal tumors were adenocarcinomas. No pathology was observed in Aqualen-fed rats untreated with the carcinogenic agent.

1,2-Dimethylhydrazine↗
PubMed1998

[The effect of cycloferon administration on the growth of transplantable tumors in rats and mice].

The influence of cycloferon and its combinations with cyclo-phosphamide on the growth of transplantable tumors was studied in rats with lymphosarcoma of Pliss and CBA and NMRI mice bearing Ehrlich's carcinoma and leukemia L1210. While cycloferon alone failed to significantly influence tumor growth, treatment with 100 mg/kg of the drug was followed by longer survival in mice with transplantable Ehrlich tumor. The highest inhibitory effect of combined cycloferon and cyclophosphamide was recorded on day 10 when tumor growth inhibition was as high as 90%. Mitotic activity of tumor was inhibited following multiple treatment with cycloferon, in combination with cyclophosphamide and cyclophosphamide alone. Survival longer than in control was registered only in animals with L1210 receiving cyclophosphamide alone or in combination with cycloferon. Cycloferon administration was shown to inhibit the growth of Pliss lymphosarcoma only within a short period after the start of the study. Combined treatment with cycloferon and cyclophosphamide produced the highest inhibition. The antitumor effect of cycloferon varied depending on tumor pattern, species and line of animals and dose and modality of administration.

Animals↗
PubMed1998

Ageing and the mechanisms of carcinogenesis: some practical implications.

Two-year protocols are commonly used for long-term assay of chemicals for carcinogenicity. However, in some cases, if animals have been exposed to tested agent from the young age and sacrificed at the age of 2, an underestimation of the carcinogenic potential of non-genotoxic agents and tumor promoters is possible. Data available show that exposure to non-genotoxic agents or tumor promoters result in tumor development in older than in young animals. Age-related accumulation of "premalignant" cells in several tissues is here discussed. Accumulation with age of spontaneous mutations or mutations evoked by endogenous mutagens can induce genome instability and, hence, increase the sensitivity to carcinogens and/or tumor promoters. It seems reasonable to recommend the use of old animals for long-term assay of compounds with suspected non-genotoxic and tumor-promoting activity. It may be important to reevaluate standard two-year protocols for long-term assay for carcinogenicity and it is recommended to keep animals for at least 30 months, better until natural death, despite non profitable from an economical point of view it is more reliable.

Aging↗
PubMed1997

Effect of melatonin and pineal peptide preparation epithalamin on life span and free radical oxidation in Drosophila melanogaster.

It was shown previously that epithalamin delays age-related changes in reproductive and immune systems and increases the life span of mice and rats. These effects could be mediated by stimulating influences of epithalamin on synthesis and secretion of melatonin and on free radical processes. A comparative study on the effect of epithalamin and melatonin on both the life span of Drosophila melanogaster (strain HEM) and on the intensity of lipid peroxidation and activity of antioxidative enzymes in their tissues was the main aim of this work. Melatonin and epithalamin was added to the nutrition medium (100 micrograms/ml) during 2-3rd age of larvas. For survival analysis the flies were passed (five coupes per vessel) each 3-7 days. Lipid peroxidation was evaluated as the level of ketodienes (KD) and conjugated hydroperoxides (CHP) in fly tissues at the age of 11 days. Activity of Cu, Zn-superoxide dismuatse (SOD) and catalase was evaluated as well. The mean, median and maximum life span (MLS) were estimated. Mortality rate (MR) was calculated as alpha in the Gompertz equation (R = Ro (exp alpha t) and mortality rate doubling time (MRDT) as in 2/alpha. These parameters in groups of male and female flies exposed to melatonin and in male flies exposed to epithalamin were no different from the parameters for controls. However, exposure to epithalamin was followed in females by a significant increase in mean life span (by 17%, P < 0.02), of median (by 26%), of MLS by 14% and by a 2.12 times decrease of MR (P < 0.01) and MRDT (by 32%) compared with female controls. The level of CHP and KD in the tissues of male control flies was 40 and 49% less than that in females and indirectly correlates with male life span. Exposure to melatonin was followed by a decrease in the level of CHP and KD in females and the deletion of sex differences in them. Exposure to epithalamin significantly decreased the level of CHP and KD in female flies compared to controls (2.3 and 3.4 times, respectively, P < 0.001). Exposure to melatonin failed to influence the activity of catalase in males but increased it in females by 24% (P < 0.02) and failed to influence SOD activity both in males and females. Exposure to epithalamin was followed by a significant increase in activity of catalse, 20% in males and 7% in females and by an increase in SOD activity in males (41%). Thus, it was shown that exposure to epithalamin significantly increases the mean life span and MLS of female D.melanogaster and slowed down their aging rate by 2.12 times. This effect is in good agreement with the inhibiting effect of epithalamin in lipid peroxidation processes in fly tissues.

Animals↗
PubMed1997

Melatonin and colon carcinogenesis: I. Inhibitory effect of melatonin on development of intestinal tumors induced by 1,2-dimethylhydrazine in rats.

The effect of pineal indole hormone melatonin on colon carcinogenesis was firstly studied in rats. Two-month-old outbred female LIO rats were weekly exposed to 15 (experiment 1, groups 1 and 2) or to five (experiment 2, groups 1 and 2) s.c. injections of 1,2-dimethylhydrazine (DMH) at a single dose of 21 mg/kg of body weight. From the day of the first injection of the carcinogen DMH, the rats from groups 2 (experiments 1 and 2) were given melatonin five days a week during the night-time (from 18:00 h to 8:00 h), dissolved in tap water at 20 mg/l. The experiment was finalized in 6 months after the first injection of DMH. In both experiments the majority of tumors were localized in the descending colon. Tumors of the small intestines developed only in rats from experiment 1. Total incidence of colon tumors as well as tumors in different parts of the colon and the mean number of tumors per rat were much higher in rats from both groups in experiment 1 than that in rats from experiment 2. In experiment 1 melatonin failed to influence the total incidence of colon tumors. However, incidence of carcinomas in the ascending colon was significantly reduced (P < 0.01). The multiplicity of total colon tumors per rat, as well as the mean number of tumors, ascending and descending colon per rat, was also decreased under the influence of melatonin (group 2 vs group 1, P < 0.01). In the same experiment, melatonin slightly decreased the depth of tumor invasion and increased number of highly differentiated colon carcinomas induced by DMH. The percentage of small tumours in the descending colon among rats from group 2 was higher than that of group 1. Treatment with melatonin was also followed by a decrease in the multiplicity of DMH-induced tumors of the duodenum (group 2 vs group 1, P < 0.05) and by a decrease in the incidence of jejunum and ileum tumors (group 2 vs group 1, P < 0.05). In experiment 2, the inhibitory effect of melatonin on DMH-induced colon carcinogenesis was much more expressed than that in experiment 1. Thus, in group 1 the incidence of total colon tumors, ascending and descending colon tumors, was significantly decreased in comparison with group 2; also melatonin reduced the number of tumors per rat in the ascending and descending colon. The number of colon tumors that invaded only mucosa was significantly higher in group 2 than in group 1, P < 0.05. The ratio of highly differentiated tumors was increased (P < 0.05) and the ratio of low-differentiated tumors was decreased (P < 0.05) in rats exposed to melatonin (group 4) as compared with group 3. The number of large size tumors in the ascending and descending colon was decreased whereas the number of small size tumors (<10 mm2) was increased in those parts of the colon that were under the influence of melatonin in experiment 2. Thus, our results demonstrate the inhibitory effect of melatonin on intestinal carcinogenesis induced by DMH in rats.

1,2-Dimethylhydrazine↗
PubMed1997

[Carcinogenesis and ontogenesis: chief trends and results of investigations].

A significant role of chemical, physical and hormonal factors modifying transplacental carcinogenesis has been established. It was found that, in tumors induced during gestation by carcinogenic agent treatment, ras oncogenes are activated due to their point mutation. The progeny of male animals exposed to radiation before mating with intact females prove to be more susceptible to such carcinogenic promoters as urethane and TPA than controls while the descendants of older males and young females are more susceptible to NMU treatment than those of young males and females. Convincing evidence of selective DNA damage being relevant to initiation of carcinogenesis was first obtained in experiments involving the use of a synthetic analog of thymidine 5-bromodesoxyuridine. Experimental treatment with carcinogenic agents and tumor promoters at different age has demonstrated age-related accumulation in different tissues of cells which have been randomly exposed to carcinogenic substances and, as a result, are pass at least one stage before complete malignant transformation. It is also assumed that such partially transformed cells are exposed to the carcinogenic effect which increases in proportion to age. Significant differences in age-related changes in the sensitivity of different tissues to the action of different carcinogens have been identified. A direct correlation between the pattern of aging delay in a population affected by a certain geroprotector and its influence on neoplasm development was established on the basis of an evaluation of the evidence on tumor incidence in experimental animals following geroprotector administration.

Age Factors↗
PubMed1997

[The effect of radiation from videoterminal of personal computer on spontaneous and estradiol dipropionate-induced carcinogenesis in mice].

Two series of experiments using female mice SHR were conducted. In the first run, the animals were exposed to radiation from a video display terminal of a personal computer (VDT), for 1 hr, 5 times a week, starting at the age of 3 months. The treatment continued until their natural death, with and without an Ergostar protective screen filter (SF). During the second run, mice were injected either 10 mkg estradiol-dipropionate (ED), subcutaneously, with 0.1 ml olive oil, or the same dose of olive oil. Beginning from the first injection of either substance, the mice started to receive VDT radiation like those of the first series did. The frequency of persistent estrus appeared to be significantly higher in the first group, irrespective of whether SF was used. The latter factor had virtually no bearing on tumor incidence rate and tumor latency period in this experiment. However, experiment 2 established a noticeable increase in incidence of mammary and ovarian tumors matched by a shorter latency period in ED- and VDT-treated animals as compared with intact controls. At the same time, mice exposed to ED and VDT+SF revealed fewer tumors of the reproductive system. It was suggested that there is no relationship between exposure to VDT and spontaneous tumorigenesis, irrespective of whether SF is used or not. However, exposure to VDT may slightly promote development of ED-induced tumors, while application of SF may moderate the process.

Animals↗