PubMed Health⌕ Search

Biomedical subjects

V N Anisimov

Publications and source records attributed to V N Anisimov.

At least 19 recordsLinked to original sources
PubMed1996

K-ras codon 12 and 61 point mutations in bromodeoxyuridine- and N-nitrosomethylurea-induced rat renal mesenchymal tumors.

The mutagenic thymidine analog bromodeoxyuridine (BrdUrd) may incorrectly incorporate opposite deoxyguanine in DNA, then pair with deoxyadenosine during subsequent replication. It appears to preferentially target the 3'-G of 5'-NGGN-3' sequences in mammalian cells in culture to induce G-->A transitions. Ras genes should therefore be vulnerable to activation by mutation at glycine codons 12 (GGT) and/or 13 (GGC) by misincorporation of BrdUrd. There is limited evidence that BrdUrd may be carcinogenic or co-carcinogenic in rats: three renal mesenchymal tumors, a tumor known to be associated with activating mutations in the c-K-ras-2 oncogene, were reported in 87 rats treated with BrdUrd alone, while N-nitrosomethylurea (NMU) alone or NMU + BrdUrd resulted in incidences of 12/52 and 26/76, respectively, against a zero incidence in untreated rats. We analyzed renal mesenchymal tumors from rats treated with BrdUrd for mutations in K-ras exons 1 and 2 and compared the prevalence and spectrum of mutations with those found in comparable tumors induced with NMU. DNAs from 22 paraffin-embedded renal mesenchymal tumors from rats treated 12-15 months earlier with BrdUrd (three specimens) or NMU (11 specimens) or both agents sequentially (eight specimens) were amplified by PCR. The base sequence of codons 12-13 and 59-63 of K-ras was determined by the dideoxynucleotide method. Sequencing results were confirmed by allele-specific oligonucleotide hybridization. Two of three tumors that appeared in rats given BrdUrd alone contained both a codon 12 GGT-->GAT transition and a codon 61 CAA-->CTA transversion. One tumor induced by NMU alone also showed a codon 12 GGT-->GAT mutation, while only wild type sequence could be demonstrated in the codon 12-13 region in the remaining ten such tumors. Three NMU-induced tumors also showed codon 61 CAA-->CTA mutations, while the remaining tumors had wild type sequence. While the GGT-->GAT transitions identified in tumors from BrdUrd-treated rats are consistent with BrdUrd mutagenesis by misincorporation, the co-occurrence of CAA-->CTA transversions, the overall low prevalence of mutations, and the lack of any difference in mutation spectrum between tumors induced by NMU and those that occurred in BrdUrd-treated rats suggests that in both groups the mutations that did occur did not result from a direct effect of either agent.

Adenine↗
PubMed1996

Study of the post-natal effects of chemopreventive agents on ethylnitrosourea-induced transplacental carcinogenesis in rats. II. Influence of low-molecular-weight polypeptide factors from the thymus, pineal gland, bone marrow, anterior hypothalamus, brain cortex and brain white substance.

The influence of the polypeptide factors extracted from thymus, pineal gland, bone marrow, anterior hypothalamus, brain cortex or brain white substance on N-ethyl-N-nitrosourea (ENU)-induced transplacental carcinogenesis was studied in rats. ENU was given to pregnant rats as a single i.v. exposure at a dose of 75 mg/kg body weight on the 21st day of gestation. The polypeptide factors were given to the offspring as a series of s.c. injections, at a dose of 0.5 mg/rat/day, starting at one or 2.5 months of age and continuing throughout the whole of post-natal life. ENU induced tumors of the brain, spinal cord, peripheral nerves and kidneys in 94-98% of the offspring exposed to the carcinogen, with an average number of 2.3-2.6 tumors per rat, and an average survival time of 294 days. Post-natal thymus factor or pineal gland factor administration was followed by an increase in mean lifespan of approximately 2 months and a significant decrease (P < 0.05) in the total tumor number per tumor-bearing rat, as well as the incidence and multiplicity of spinal cord tumors. Pineal gland factor also decreased the incidence of peripheral nerve and kidney tumors and their number per tumor-bearing rat. Brain cortex factor and brain white substance factor treatment was followed by a decrease in total tumor multiplicity of 1.2- to 3.3-fold, and a decrease in incidence of brain tumors of 10 to 33% per rat in comparison to the controls. Brain cortex factor also decreased the total tumor incidence. At the same time, brain white substance factor administration increased the incidence of peripheral nerve tumors and decreased the mean lifespan. Both bone marrow factor and anterior hypothalamus factor did not have any modifying effects on any of the ENU-induced tumors and mean lifespan. Thus, our results show the possibility of attenuation of transplacental ENU-induced carcinogenesis with post-natal administration of some polypeptide substances.

Animals↗
PubMed1996

[Effect of radiation emitted from personal computer terminal on urethan-induced lung tumors in mice].

Female SHR mice were injected intraperitoneally 0.2 ml of 1% solution of urethan on days 1, 8, 54 and 61 of the experiment. Beginning from day 1, they were exposed to radiation emitted from the video terminal of the EGA/PC/AT-286 (personal computer), for 1 hr, 5 times a week. The exposure was conducted with or without the Ergostar G-14 protective filter. The distance between the PC screen and the cage bottom was 38 cm. It was found during the 12 months of the experiment that the lifespan of urethan-injected animals was somewhat shorter as a result of the exposure. A significantly higher frequency of all or only malignant tumors of the lung and uterine polyps was recorded in urethan- and irradiation-treated mice than in non-irradiated controls. However, irradiation of urethan-treated animals from a filter-protected screen was followed by a significant decrease in frequency of incidence of all neoplasms and multiple tumors of the lung, as compared with those exposed to unfiltered radiation. It is suggested that long-term exposure to PC-emitted irradiation may cause slight stimulation of urethan-induced carcinogenesis of the lung. The Ergostare filter was found to make no contribution to carcinogenesis. It is also thought that the urethan dose was too large and the entire model--too rigid to adequately assess the PC influence on neoplastic formation.

Animals↗
PubMed1996

[Skin carcinogenesis induced be neonatal administration of 5-bromo-2'-deoxyuridine and subsequent treatment with 12-O-tetradecanoylphorbol-13-acetate in mice].

Male and female SHR mice were injected, subcutaneously, 1 mg of 5-bromo-2'-deoxyuridine (BrdUrd) or 0.05 ml of distilled water on days 1, 3 and 7 after birth and painted with 6.15 mkg of TPA dissolved in 0.1 ml of acetone, or acetone alone, twice a week, for 24 weeks, starting at the age of 15 weeks. The animals were followed up for 20 weeks after stopping TPA painting. Skin tumors emerged in TPA-treated animals only. TPA painting was followed by skin papilloma development in 20.9% of males and 36.6% females injected distilled water neonatally, tumors regressing in 88.4% of males and 85.4% of females by the end of the experiment. With combined treatments with BrdUrd and TPA, skin papilloma incidence was 56.5% in males and 52.6% in females, tumors persisting in 52.2% and 39.6%, respectively, until the end of the experiment.

Animals↗
PubMed1996

[Effect of melatonin on 1,2-dimethylhydrazine-induced intestinal tumors in rats].

Fifteen doses of 21 mg/kg body weight of 1,2-dimethylhydrazine (DMH) were injected into 48 female rats at one-week intervals. Controls included 25 animals while 23 received 20 mg/l of melatonin with drinking water, 5 times a week, at night-time, for 6 months, beginning from the day of the first injection. Although malignancies of large bowel developed in all animals, multiple tumors in the melatonin group were significantly fewer than in the rats treated with DMH alone (6,0 and 9,9 respectively; p < 0,001). Similarly, melatonin treatment was followed by a significantly lower frequency of tumor development in the ascending colon as well as fewer multiple neoplasms of the ascending and descending colon. Melatonin was also shown to inhibit carcinogenesis in the small intestine. It is suggested that the antitumor effects of melatonin is due to its antioxidant properties.

1,2-Dimethylhydrazine↗
PubMed1995

Carcinogenesis induced by neonatal exposure to various doses of 5-bromo-2'-deoxyuridine in rats.

Male and female outbred LIO rats were exposed to subcutaneous injections of 3.2 mg 5-bromo-2'-deoxyuridine (BrdUrd), on day 1; days 1 and 3; or days 1, 3, 7, and 21 following birth. The mean life-span decreased by 40.9, 31.2 and 38.9% in males exposed to 1, 2 or 4 injections of BrdUrd, respectively, and by 22.9, 10.5 and 23.4% in females, respectively, compared to the controls. The agent increased the population aging rate of the exposed male and female rats. Total tumor incidences in males exposed to 0, 3.2, 6.4 or 12.8 mg of BrdUrd were 21.1, 27.3, 40.0 and 33%, respectively, and in the females 44.3, 54.5, 48.1 and 56.3%, respectively. Only the largest dose of BrdUrd significantly increased the tumor incidence in the exposed rats as compared to the control ones (P < 0.05). However, tumor latency was shorter in any group of rats exposed to BrdUrd, as compared to the control one. The exposure to 0, 1, 2 or 4 injections of BrdUrd was followed by the development of testicular Leydigomas in 0, 0, 28 and 12% of males, respectively. There was no organ or tissue target for BrdUrd in the females. However, the development of tumours not typical for the rats and the widening of tumor spectrum was observed in the female rats exposed to the agent.

Animals↗
PubMed1995

Effect of aging and interval between primary and secondary treatment in carcinogenesis induced by neonatal exposure to 5-bromodeoxyuridine and subsequent administration of N-nitrosomethylurea in rats.

LIO rats were exposed to s.c. injections (3.2 mg) of a synthetic analogue of thymidine, 5-bromo-2'-deoxyuridine (BrdUrd) on the 1st, 3rd, 7th and 21st days of life and at the age of 3 or 15 months they were i.v. injected with N-nitrosomethylurea (NMU) at a single dose of 10 or 50 mg/kg or with solvent. It was shown that early neonatal exposure to BrdUrd was followed by the increase in the incidence of tumor development and by the decrease of their latency. The carcinogenic effect of NMU alone correlated with the dose of the carcinogen in 3-month-old rats total and malignant tumors and tumors of some localization was decreased in the elder ones, but survival of tumor-bearing rats was decreased in the elder group as compared to the younger one. These data suggests the age-related decrease in both the carcinogenic effect of NMU and in the number of events which are necessary for a tumor development. The exposure to BrdUrd was followed by the increase in the susceptibility of rats to subsequent carcinogenic effect of NMU injected at the doses of 10 or 50 mg/kg into 3- and 15-month-old rats, mostly to the tissues being target to NMU. Our data have demonstrated that the exposure to BrdUrd in the early life was followed by the irreversible initiating effect which persists over a long time in a several tissues.

Aging↗
PubMed1995

N-nitrosomethylurea-induced carcinogenesis in the progeny of male rats of different ages.

Three-month-old male and 3-month-old female LIO rats as well as 25-month-old males and 3-month-old females were mated and at the age of 3 months their progeny were exposed to a single intravenous injection of N-nitrosomethylurea (MNU) at the dose of 20 mg/kg of body weight or solvent. Animals were under observation during 18 months after injection of the carcinogen. There was no significant difference in spontaneous tumor incidence between progeny of young and old male rats. At the same time, the susceptibility to the carcinogenic effect of NMU in the male and female progeny of old males was slightly but significantly increased in comparison to the progeny of young males. Mesenchymal kidney tumors were discovered in the NMU-treated male progeny of old males but not in the male progeny of young male rats. In females, the incidence of mesenchymal kidney tumors in the NMU-treated progeny of young and old males was 7% and 20%, respectively, and the mean survival times of these tumor-bearing rats was 4 months shorter in the last group. The data obtained are in agreement with the observation on germ-line transgeneration transmission of predisposition to carcinogenesis.

Animals↗
PubMed1994

[Effects of light deprivation on carcinogenesis induced by N-nitrosomethylurea in female rats].

One month-old female rats were blinded by surgery and received single intravenous injections of 50 mg/kg body weight of N-nitrosomethylurea (NMU) two weeks later. Simultaneously, normal animals were injected an identical dose of NMU. The frequency of NMU-induced neoplasms in blind rats was 33% vs. 75% in control (P < 0.05), with neoplastic development latency being longer as compared with controls. The frequency of mammary gland adenocarcinoma, leukemia and adenoma of the pituitary and thyroid gland in blind rats was significantly lower while mammary gland fibroadenoma was more frequent than in intact animals. Carcinogen-treated blind animals survived much longer (448 +/- 21 days) than normal controls (284 +/- 22 days) (P < 0.001). The frequency of spontaneous neoplasms in blind and normal rats was identical. The inhibitory effect on carcinogenesis seems to be due to enhanced functional activity of the pineal gland in blind animals.

Adenocarcinoma↗
PubMed1994

[The preventive medical aspects in ensuring efficiency and safety in the operation of a fire-fighting and accident-rescue service].

On the basis of national and foreign experience on liquidation of the consequences of natural calamities and catastrophies the article shows the necessity to introduce a course of medical training into the program of studies for the specialists of fire-fighting and rescue services of the Ministry for Internal Affairs of the Russian Federation (MIARF). This training will ensure these specialists with adequate skills of primary medical and predoctor care in disaster situations. The article contains basic items of the Program of medical training for the students of the St. Petersburg Higher Fire-Fighting Technical School of MIARF which was included into curriculum planning in 1992.

Accidents↗