[Effect of epsilon-aminocaproic acid, cyclophosphamide and their combination on the growth of autochthonous sarcomas of mice induced by benzo(a)pyrene].

Antifibrinolytic drug epsilon-aminocaproic acid as a therapeutic form (5% solution in saline) was tested for antitumor activity in the autochthonous subcutaneous tumors of mice, induced by benzo (a) pyrene, in monotherapy mode (instead animals received drinking water) and in combination with cyclophosphamide, which was administered once intraperitoneally in the dose of 200 mg/kg. In the control groups, treated with drinking water and saline solution instead of water, there was no stabilization and reduction in tumor volume, while in the groups receiving epsilon-aminocaproic acid, cyclophosphamide and their combination statistically significantly in comparison with the control groups there was increased the proportion of tumors with not changed or reduced volume; epsilon-aminocaproic acid enhanced the antitumor effect of cyclophosphamide. The data obtained are for further study of the antitumor effect of epsilon-aminocaproic acid.

[The effect of sodium fluoroacetate and metformin on the antitumor activity of cyclophosphamide on the autochthonous mice sarcoma model].

Previously it was found that sodium fluoroacetate (SF) inhibited the growth of the Ehrlich cancer by means of monotherapy and enhanced the antitumor effect of cyclophosphamide (CP) in experiments with autochthonous subcutaneous tumors induced by benzo (a) pyrene. In this study a comparison of the antitumor activity of SF and metformin showed that both substances did not have significant effect in monotherapy but enhanced the effect of CP, increasing the percentage of tumors with the same or reduced volume. Besides, SF, unlike metformin increased the average duration of effect. The data obtained promoted further study of the mechanism of the antitumor effect of SF and the search effective combination with already known antitumor drugs.

[Effect of plastoquinone derivative SkQ1 on benzo(a)pyrene-induced soft tissue carcinogenesis].

Ninety female SHR mice were subcutaneously injected with a single dose of 2 mg benzo(a)pyrene (BaP) dissolved in 0.2 ml of vegetable oil. Since the next day after BaP injection mice were started to treat with mitochondria-targeted antioxidant SkQ1 at the doses of 5 and 50 nmol/kg/day in drinking water. Control animals received tap water. Study was finished by 358th day. Number of tumor-bearing mice increased in all groups exposed to BaP but retarded since 20th week in SkQ1-treated groups in comparison with control. Maximal tumor volume gain was observed in control mice resulting in premature death. By the 30th week of study only 20% of control animals survived, whereas SkQ1 treatment increased survival up to 30% at the dose of 5 nmol and 40% at the dose of 50 nmol. By the 40th week mean tumor volume in 5 and 50 nmol SkQ1-treated mice was 13 and 21 cm3 respectively, whereas in control--40 cm3. In SkQ1-treated mice pneumonia was observed rarely as compared with controls. It could be supposed, SkQ1 at the doses of 5 and 50 nmol/kg/day retarted BaP-induced soft tissue carcinogenesis in SHR mice.

[Effect of sodium fluoroacetate on Ehrlich solid tumor and autochthonous sarcoma growth in mice].

Due to biochemical characteristics of toxic action of fluoroacetate on energetics and metabolism of cells, including tumor cells, it was interesting to testify sodium fluoroacetate (SFA) for its antitumor activity in vivo. We have estimated that SFA significantly inhibits growth of Ehrlich tumor carcinoma. In experiments with autochthonous induced by benzo[a]pyrene subcutaneous tumors, SFA was not active in monotherapy regime, though potentiated antitumor effect of cyclophosphamide, significantly increasing the relative number of mice with stabilized or decreased tumor volume as well as the duration of this effect. The data obtained render basis for additional studies of mechanism of antitumor effect of SFA.

[The effect of SSH&H on the lifespan and spontaneous cancer development in transgenic mice with HER-2/neu mutation].

10 months old mice receiving SSH&H with daily food increased the lifespan in comparison to the control group. The maximal lifespan was increased by 1,6 months. For the long-living 10% group the mean lifespan increased by 8,7% compared to the control group (p<0,05). The mammary gland neoplasia rate was the same in both groups. The mean latent tumor development period duration, number and size of the tumors were also similar. There was a tendency to lower lung metastases rate in the experimental group. The cumulative neoplastic frequency curve for the experimental group was shifted to the right in comparison to the control group curve giving evidence to the inhibitory effect of SSH&H on the neoplastic rate in transgenic mice with HER-2/neu mutation.

[Metformin effect on urethane-induced tumorigenesis in mice].

Sixty one male 129/Sv mice were exposed to a single intraperitoneal injection of 1 g per kilo of urethane dissolved in 0.9% normal saline. Starting the next day from the injection the study group mice were given 1200 mg metformin per liter of drinking water 5 days a week for 26 weeks. The control group mice received pure drinking water. Six months after the urethane treatment the mice were killed and the morphology samples were taken. Twenty five of 31 (96.7%) control group mice developed tumors (lung adenomas and thymic lymphomas), while tumor development was observed in 25 of 31 (80.7%; p<0.05) mice exposed to metformin. Solid or trabecular lung adenomas developed in 90% of the control group mice and in 77% of the metformin group mice (p=0.119). Therefore, it is a first evidence of tumor-inhibitory effect of metformin in mice.

[Kinetic features of ascites and solid Ehrlich tumors].

Such biological parameters as tumor volume, Ki-67 and p53, which characterize the development of ascites and solid tumor of Ehrlich were evaluated. The kinetic curve of growth of ascites tumor was S-shaped (Gomperts) while that of the solid one--cubic (Speer-Retsky). Ki-67 expression level was found to be in cyclic correlation with duration (3 and 6 day intervals) which might be worth considering when working out therapeutic procedure. Moreover, no increase in cell death was observed when tumor growth slowed down.

[Inhibition of 1,2-dimethylhydrazine-induced carcinogenesis in rat gut by the antidiabetic drug Diabenol]. / Tormozhenie antidiabeticheskom preparatom Diabenol kantserogeneza kishechnika, indutsiruemogo 1,2-dimetilgidrazinom u krys.

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.

[Effect of antidiabetic drug diabenol on parameters of biological age, life span and tumor development in NMRI and HER-2/neu mice]. / Vliianie antidiabeticheskogo preparata diabenol na pokazateli biologicheskogo vozrasta, prodolzhitel'nost' zhizni i razvitie novoobrazovanii u myshei NMRI i HER-2/neu.

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

[Susceptibility of wild and knockout p53 FVB/N line mice to benz(a)pyrene-induced subcutaneous sarcoma]. / Chuvstvitel'nost' mishei linii FVB/N (dikogo tipa i nokautnykh po p53) k induktsii podkozhnykh sarkom benz(a)pirenom.

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.

[The effect of melatonin on the indices of biological age, on longevity and on the development of spontaneous tumors in mice]. / Vliianie melatonina na pokazateli biologicheskogo vozrasta, prodolzhitel'nost' zhizni i razvitie spontannykh opukholei u myshei.

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.

[New means for the prophylaxis of colon cancer with the use of beta-glucuronidase inhibitors]. / Novye vozmozhnosti profilaktiki raka kishechnika s ispol'zovaniem preparatov - ingibitorov beta-gliukuronidazy.

Experiments involving the use of 1,2-dimethylhydrazine-induced colonic tumors in rats showed long-term treatment with a newly synthesized drug EDE-10g to inhibit an enzyme of enteric beta-glucuronidase, to suppress carcinogenesis and to prolong lifespan of animals.

[The possible carcinogenic properties of riboxin (inosie F)]. / Issledovanie vozmozhnykh kantserogennykh svoistv riboksina (inosie F)

Long-term treatment of rats and mice with riboxyn failed to reveal the carcinogenic effect of the drug. Chronic experiments showed the drug to improve resistance of the animals to intercurrent infections.

[Possibility of using fish and amphibians for detecting the carcinogenic action of nitrosomorpholine and its chemical precursors]. / Vozmozhnost' ispol'zovaniia ryb i amfibii dlia vyiavleniia kantserogennogo deistviia nitrozomorfolina i ego khimicheskikh predshestvennikov.

When dissolved in water nitrosomorpholine induced in frogs Rana temporaria and aquarium fish adenomas and cancer, hemocytoblastosis, adenomatous polyps and adenocarcinomas of the intestine, mesenchymomas. A combined action of sodium nitrite and morpholine would induce the tumors concerned, but taken separately NN and M produced only a toxic effect. The morpholine nitration appears to proceed both endogenously and directly in water. It seems rational to use animals of the aqueous medium as an indicator of nitrosoamines and their precursors contamination of hydrosphere.