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Biomedical subjects

M A Zabezhinskiĭ

Publications and source records attributed to M A Zabezhinskiĭ.

At least 19 recordsLinked to original sources

[Effect of epitalon and melatonin on life span and spontaneous carcinogenesis in senescence accelerated mice (SAM)].

Female senescence accelerated mice SAMP-1. (prone) and SAMR-1 (resistant) were exposed 5 times a week monthly to melatonin (with drinking water 20mg/ml during the night hours) or to s.c. injections of epitalon (Ala-Glu-Asp-Gly) at a single dose 1mkg/mouse. Control mice were intact or exposed to injection of 0.1 ml normal saline. The body weight and temperature, food consumption, estrous function were monitored regularly. The life span and tumor incidence were evaluated as well. As age advanced, the weight increased whereas food consumption and body temperature did not change. There was no significant substrain difference in these parameters. Exposure to melatonin or epitalon also failed to influence those indices. As age advanced, the incidence of irregular estrous cycles increased both in SAMP-1 and SAMR-1, whereas the treatment with both melatonin and epitalon prevented such disturbances. SAMP-1 revealed some features of accelerated aging as compared to SAMR-1. The mean life span of the 10% of the last survivors among treated SAMP-1 was shorter than that of SAMR-1, aging rate increased and mortality doubling time decreased. There was a direct correlation between body mass of the two substrains at the age of 3 and 12 months matched by body mass increase and longer life span. Melatonin or epitalon treatment was followed by longer mean and maximum survival in the 10% of the last survivors among SAMP-1. Melatonin involved decreased aging rate and increased mortality doubling time. Malignant lymphomas predominated in SAM without any significant difference in frequency between the substrains. While melatonin failed to influence tumor incidence or term of detection in SAMP-1, neither did epitalon affect frequency. However, it was followed by longer survival in tumor-free animals. No link between melatonin or epitalon treatment, on the one hand, and carcinogenesis, on the other, was reported in SAMR-1.

Aging↗

[Effect of light deprivation on homeostasis, life span and development of spontaneous tumors in HER-2/neu transgenic mice].

Twenty five female HER-2/neu transgenic mice (FVB/N), aged 2 months, were surgically deprived of lighting; 30 intact transgenic mice, kept under standard conditions, were in control. Light deprivation was followed by inhibited intake of feed, decreased body mass and delayed age-associated estral disorders, as compared with control. Mean survival rate among experimental mice was higher by 13.5% than in control (p 0.001). Mean life span among the last surviving 10% of the experimental mice was longer than in control by 21.5% while maximum life span--by 21%. Although the number of tumor bearers under 7 months in the study group was twice that in control (p<0.05), they had almost equalized by the end of the experiment. The number of multiple malignancies and the size of tumor and metastases to the lung increased too.

Animals↗

[Inhibition of 1,2-dimethylhydrazine-induced carcinogenesis in rat gut by the antidiabetic drug Diabenol].

Diabenol, a new Russian antidiabetic drug, was used to investigate its effect on 1,2-dimethylhydrazine (DMH)-induced carcinogenesis in rat large gut. Five doses of 21 mg/kg DMH were injected at an interval of one week. Administration of 10 mg/kg diabenol with drinking water had no effect on either body mass or feed and water consumption. Yet, it was followed by a significant decrease in tumor incidence (4.22 vs. 5.77 tumors per tumor-bearers), frequency of neoplasms in the ascending colon (40.0% vs. 89.5%) and in their number (0.60% vs. 1.63 tumors per rat in a group). In the other groups, those indices tended to be still lower. Another tendency characteristic of the experimental group was a significantly high percentage of exophytic tumors (76.3% as compared with 50% in control) consisting of well-differentiated cells (47.4% and 14.7%, respectively) and with predominantly shallow invasion into the gut wall. Our results suggest the ability of the drug to inhibit DMH-induced carcinogenesis in the rat large gut.

1,2-Dimethylhydrazine↗

[Effect of antidiabetic drug diabenol on parameters of biological age, life span and tumor development in NMRI and HER-2/neu mice].

The effect of new antidiabetic drug Diabenol [9-diethylaminoethyl-2,3-dihydroimidazo-(1,2alpha) benzimidazol dihydrochloride] on life span and spontaneous tumor incidence in NMRI and transgenic HER-2/neu mice was studied. Female NMRI and transgenic HER-2/neu mice were given diabenol with drinking water (0.1 mg/l=approx. 10 mg/kg of b.w.) 5 times a week since the age of 2 months until natural death. The treatment with the drug failed influence body weight gain dynamics, food and water consumption and the body temperature in NMRI mice. Diabenol treatment slowed down age-related disturbances in estrous function and increased life span of all and 10% most long-living NMRI mice. The treatment with diabenol inhibited spontaneous tumor incidence (mammary gland and lymphomas mainly) and increased the mammary tumor latency. Dibenol treatment slowed down age-related changes in estrous function in HER-2/neu mice, failed influence survival of these mice and slightly inhibited the incidence and decreased the size of mammary adenocarcinoma metastases into the lung. Thus, long-term treatment with diabenol is safe and non-toxic in mice. The drug increases survival and inhibits spontaneous carcinogenesis in mice

Adenocarcinoma↗

[Basic directions and prospects for international collaboration in gerontology. Role of the International Association of Gerontology].

The overview presents data on the international collaboration in gerontology in the following spheres: 1) organizational basis of collaboration; 2) coordination of research; 3) coordination in the training of specialists; 4) collaboration in the organization of geriatric services; 5) collaboration in social care for the elderly. Role of the International Association of Gerontology and other international organizations in the promotion of gerontology and geriatrics in each of these spheres is shown by the example of Russia.

Aged↗

[Effect of Epitalon and Vilon treatment on mammary carcinogenesis in transgenic erbB-2/NEU mice].

Female transgenic FVB mice transfected with the mammary erbB-2/neu oncogene were injected 0.1 ml 0.9% solution of sodium chloride (control), 1 meg Vilon peptide (Lys-Glu) or Epitalon peptide (Ala-Glu-Asp-Glu), s.c., 5 days in succession once a month, beginning from the age of 2 months. The characteristics of mammary tumor induction in the control and experimental groups did not differ until the age of 9 months. Later on, Epitalon-treated mice revealed distinct inhibition of carcinogenesis. One tumor per animal was detected in 7% (control), 4% (Vilon) and 16% (Epitalon) (p < 0.05). Two or more tumors per animal were in 75%, 95% and 56%, respectively (p < 0.05). Largest diameter of mammary adenocarcinoma in the Epitalon group was smaller than in controls by 33% (p < 0.05). Although the number of mice with metastases to the lung in all three groups was practically identical, their incidence in the Vilon group was 2.6 times higher than in Epitalon-treated animals (p < 0.05). Largest diameter of metastasis in the Epitalon group was the smallest, too. Our data point to inhibition of mammary carcinogenesis by Epitalon in transgenic erbB-2/neu mice.

Adenocarcinoma↗

[Susceptibility of wild and knockout p53 FVB/N line mice to benz(a)pyrene-induced subcutaneous sarcoma].

Susceptibility to benz(a)pyrene (BP) has been compared between wild and knockout p53 homo- and heterozygous FVB/N, C57BL/6 and NMRI line mice. Each group included 34-80 animals. Each animal was injected 2 mg BP, s.c., in sunflower oil solution. The animals were followed up for 24 weeks. Fibrosarcomas arose at the site of injection in: wild FVB/N line mice--93%; FVB/N heterozygous--100%; p53 homozygous knockout--95%; C57B1/6--84%, and NMRI mice--83%. Mean latent period was 68, 66, 69, 112 and 109 days, respectively. Hence, FVB/N line mice developed tumors much earlier than C57B1/6 or NMRI did, suggesting their higher susceptibility to carcinogenic BP injection. No significant difference in susceptibility to carcinogen versus p53 expression was reported.

Animals↗

[Effect of pineal peptide on parameters of the biological age and life span in mice].

Female CBA mice were injected with s.c. synthetic tetrapeptide Epithalon from a 6-month age until death. The drug failed to affect the body weight or food consumption, physical activity or behavioural parameters. However, it slowed down the age-related switching off of the estrus function, decreased body temperature, decelerated free redical processes, prolonged the mice life span with an accompanying drop in spontaneous tumour incidence.

Aging↗

[Morphologic study of renal carcinogenesis in rats induced by dimethylnitrosamine].

109 five-month-old albino non-inbred male rats received a single i.p. injection of dimethylnitrosamine (20 mg/kg b.w.) for selective induction of renal epithelial tumors. Forty controls were injected isotonic solution. The animals were autopsied 3-12 months later. Renal cell adenomas were found in 5 rats, mesenchymal renal--6. Renal tumor incidence increased during the experiment reaching 38.5% at month 12. No tumors were detected in controls. To summarize, our experiment failed to induce renal cell tumors only.

Adenoma↗

[Metabolic effect of tobacco smoke and "switching" the estrogen effect: mechanism of increased genotoxicity].

Earlier studies demonstrated dynamic changes in the hormonal and genotoxic effects of estrogens and a decrease in estradiol concentrations and/or aromatase (estrogen synthetase) activity in the uterine tissue in rats exposed to tobacco smoke (TS) and in endometrial and breast tumor tissues of female smokers. This study was the first to reveal an elevation in the excretion of 2- and 4-hydroxyestrogens in smoking postmenopausal women receiving estrogen-replacement therapy, an increase in estrogen-2-hydroxylase activity in the breast and endometrial tumors of the smokers, and no signs of higher aneuploidy frequency in the cervicovaginal epithelium of mice exposed to TS + estrogens. Thus, it can be concluded that there are different stages of endocrine and genotoxic effects of a TS + estrogen combination which may be related to the specific mechanisms and types of hormonal carcinogenesis. A combination of estrogens and smoking induces such variants of DNA damage, which are mediated mainly through the metabolism of catecholestrogens/free radical formation and not through increased or incorrect (aneuploidy) proliferation.

Adult↗

[The effect of melatonin on the indices of biological age, on longevity and on the development of spontaneous tumors in mice].

Fifty female CBA mice were given melatonin with drinking water (20 mg/l) for 5 consecutive days monthly, beginning from the age of 6 months, until natural death. Another 50 intact mice were used as controls. Melatonin failed to significantly influence body weight or food consumption. Age-related switching-off of estrus function was delayed, body temperature decreased. Somewhat decreased motor activity did not affect physical one or endurance. Increase in life span led to higher spontaneous tumor incidence. Another experiment using 20 animals of the same line showed melatonin to inhibit free-radical processes. A conclusion was drawn that caution should be exercised before melatonin is recommended for long-term administration as a geroprotector.

Aging↗

[Effect of cycloferon on the evolution of cervical and vaginal cancer in mice].

7,12-dimethylbenz(a)anthracene (DMBA) was given by tampon intravaginally to 198 mice CBA (9 groups), twice a week, for 2 months, to induce cervical and vaginal tumors. Cycloferon (CF)--an interferon inductor--was injected in study group animals subcutaneously and/or introduced into the vagina by smear, in 2-month courses. CF was given during DMBA treatment or after it. Controls were injected saline solution, sc, and/or received placebo smears, i.v. The experiment was run for 6 months. Tumor incidence in controls was 35-70%. Carcinogenesis tended to slow down when CF was given during DMBA treatment. Neoplasia was found in 38-57%. More marked anticarcinogenic effect was registered in animals receiving CF on termination of DMBA application: tumor frequency dropped to 29-41%, with malignant tumor number significantly reduced.

9,10-Dimethyl-1,2-benzanthracene↗

[The use of cycloferon in experimental radiotherapy of tumors].

The biological activity of cycloferon (CF) used in interferon manufacture has been investigated for its therapeutic and prophylactic properties which may be used for radiotherapy of glioma. It was demonstrated in experiments on rats that use of CF is most effective at an early stage of irradiation due to decrease in tumor mass which does not occur in case of irradiation alone. When used at a later stage, CF caused certain hematological indices of immunity to rise. CF did not produce an antitumor effect of its own. It successfully competed with Leukomax when used to bring blood indices in irradiated tumor-bearing animals back to normal.

Acridines↗

[Experimental investigation of 2,2'-diamino-1,1'-dinaphthyl in rats and mice].

Carcinogenicity of 2,2'-diamino-1,1'-dinaphthyl has been investigated in chronic experiments on LIO rats and CC57 mice. Single doses of 20 mg were given to rats and 1-5 mg--mice. Subcutaneous injections were followed by sarcoma development on injection site in 90% of male rats and 31%--females. Female rats (46%) also revealed multiple benign tumors of the mammary gland. Such tumors alone were detected in females (44%) receiving the agent with feed. All mouse males and 71-100% of females developed hepato- and cholangiocellular tumors as well as hepatic hemangiomas following subcutaneous injection, oral or skin administration. 2,2'-diamino-1,1'-dinaphthyl proved a potent carcinogenic agent; it is suggested that it might metabolize to such carcinogen as 2-naphthylamine.

Animals↗

[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↗