[Production of nitric oxide metabolites during transplanted tumors growth with different metastatic potential].

The endogenous formation of metabolites of NO - nitrite (NI), nitrates (NA) and volatile nitrosamines in the body, tumor tissue and by abdominal cavity by macrophages for dynamics was investigated in mice F1(C57BlxCBA), Balb/c and BDF with subcutaneous transplanted tumors (Erlich carcinoma - EC and metastatic Lewis lung carcinoma - LLC). It was shown that growth of EC was accompanied by a statistically significant increase in the concentrations of NI and NA in tumor tissue to (7.3±4.67)'10-6 - (7.8±2.57)'10-5 (mol/kg) for the first three weeks and a sharp increase in urinary excretion of NI and NA. The maximum total concentration of NI and NA - (3.,6±0.46)'10-5 in tissue LLC was registered during the early stage of the tumor growth (7 days); it later declined, negatively correlating with the mass of the tumor. NI secretion by abdominal cavity macrophages demonstrated statistically significantly decrease at the stage of intensive growth LLC (14, 21 days). The tissue of EC contained varied concentration of cancerogenic N-nitrosodimethylamine and N-nitrosodiethylamine at all investigated time points. Thus, the ability of different gistogenesis tumor tissue to synthesize metabolites NO depended on time parameters and was more pronounced for EC, than LLC.

Production of nitrogen oxide derivatives under the influence of NO-synthase inhibitors and natural compounds in mice with transplanted tumors.

AIM: The aim of the present study was to investigate the dynamics of nitric oxide derivative (NOD) formation in mice with transplanted tumors and to analize whether synthetic NO-synthase inhibitors, NO-donors and natural compounds could modulate NOD synthesis. MATERIALS AND METHODS: In the study F(1)(C(57)BlxCBA), CBA/Lac, BDF and Balb/c mice were used. Endogenous NOD synthesis in mice with transplanted Ehrlich carcinoma (EC) and Lewis lung carcinoma (LLC) was estimated by measuring urine nitrates (NA) and nitrites (NI) excretion and their concentration in tumor tissue determined by cadmium-reduction method. RESULTS: It is shown that EC development is accompanied by increased endogenous NOD formation whereas LLC growth - by its decrease. Total NOD excretion with urine in EC-bearing mice during tumor development was in the range of 1.1x10(-7)-7.0x10(-6) mol/kg body weight that was 1.7-6.8 times higher than that in LLC-bearing mice. Treatment of EC-bearing animals with N(ώ)-nitro-L-arginine and aminoguanidine resulted in decreased NOD formation causing moderate tumor growth retardation. Effect of treatment with nitroprusside was shown to be dependent on the rout of its administration and dosage. Treatment of EC-bearing mice with picnogenol, tannic acid, spirulina and paprika enriched with selenium resulted in tumor growth inhibition at the early stage of EC growth accompanied by stimulation of endogenous NOD formation. CONCLUSION: Regulation of endogenous NOD formation towards normal physiological levels or hyperproduction of these compounds may result in tumor growth suppression.

[Effect of sweet pepper, enriched with selenium, on the transplantable Ehrlich carcinoma in mice].

Effect of sweet pepper enriched and non-enriched with Se on Ehrlich carcinoma growth at Balb/c mice was investigated. 1000 mg/kg of both preparations of sweet pepper (per os administration for mice of 9 months age) inhibited an early stage of tumour growth on 42-62% and 37-65% respectively. No effect on tumour growth was registered for 4 months mice.

[Sodium nitrite-induced potentiation of spontaneous and 1,2-dimethylhydrazine-induced carcinogenesis in male mice F1 (C57 B1xCBA)]. / Potentsiruiushchee deistvie nitrita natriia na razvitie spontannykh i indutsirovannykh 1,2- dimetilgidrazinom opukholei u myshei-samtsov F1 (C57Bl x CBA).

Chronic sodium nitrite (SN) treatment potentiated spontaneous and 1,2-dimethylhydrazine (DMH)-induced carcinogenesis. Mice injected with SN alone showed a higher incidence of leukemia and lung cancer than in controls. Combined treatment with DMH and SN induced most of benign and malignant tumors (hepatic hemangioendothelioma, hepatocarcinoma, renal adenoma, etc.). The difference in the numbers of DMH- and SN-induced tumor bearers was not significant until a concentration of 500 mg/l was reached (64.7%). The level of multiple tumor incidence increased when SN 50 and 500 mg/l was used. Unlike DMH alone, cumulative incidence of DMH-specific tumors and leukemia after combined treatment was higher. An evaluation of cumulative incidence and relative risk established an indirect but positive correlation between SN dose, on the one hand, and spontaneous and induced carcinogenesis, on the other. The strongest carcinogenic effect was reported when DMH was used in combination with SN 500 mg/l. Our data confirmed the carcinogenic hazard of chronic exposure to SN which increased when in combination with that to a specific carcinogenic substance.

[Modifying effect of nitrites on pulmonary blastogenesis and viral leukogenesis in mice: role of nitric oxide and dioxide]. / Modifitsiruiushchee deistvie nitritov na legochnyi blastomogenez i virusnyi leikogenez u myshei: vozmozhnaia rol' okisi i dvuokisi azota.

The long-term effects of sodium nitrite (NaNO2) on carcinogenesis induced by urethane (total dose 1.0 mg/g body weight) in low-grade cancer F1 (C57BLxCBA) and high-grade A/Snell mice and on viral (Rausher leukemia virus) leukomogenesis in Balb/c mice. The murine intake of NaNO2 with water (50 mg/l) causes a statistically significant increase in the number of adenomas in the lung. Examining the mechanism of conversion of NO2- to NO led to the assumption that the free radical compounds NO and NO2 are involved in the potentiating action of NO2 on blastomogenesis. The use of the oxidant emoxypine (3-hydroxypyridine) confirmed the above. The role of NO and NO2 in the intracellular processes under the modifying effects of nitrites and nitrates on blastomogenesis is analyzed.

[Study of cancerogenic effect of 4-amino-1,2,4-triazole in chronic experiments]. / Eksperimentalnoe izuchenie kantserogennogo deistviia 4-amino-1,2,4-triazola v khronicheskikh éksperimentakh.

Results of carcinogenic testing of 4-amino-1,2,4-triazole (AT) in chronic experiments is presented. The testing did not reveal carcinogenic properties of this substance in rats but showed carcinogenicity in F1 mice. AT can be characterized as a substance with limited evidence of carcinogenicity.

[The carcinogenic activity of N-nitroso-N-ethylurea in kidney organ cultures of mice exposed transplacentally to cobalamin coenzymes and folinic acid]. / Kantserogennaia aktivnost' N-nitrozo-N-étilmocheviny v organnykh kul'turakh pochek myshei pri transplatsentarnom vozdeistvii s kobalaminovymi kofermentami i folinovoi kislotoi.

Preneoplastic changes in organ cultures of mouse embryonic kidney (OCEK) under transplacental N-nitrosoethyl urea (ENU) did not increase under the influence of Ado-Cbl. The frequency of focal proliferation in OCEK under transplacental influence of Ado-C bl and ENU was 2.2 times less than the combination of carcinogen with MeCbl (32.2% and 71.9%, respectively, P less than 0.01). The number of DNA-synthesising epithelial cells in OCEK were less under transplacental influence of Ado-Cbl (8.6 +/- 1.4%) than in MeCbl or FA (19.4 +/- 1.8% and 16.2 +/- 1.3% respectively, P less than 0.01).

[The modifying influence of adenosylcobalamin on the transplacental carcinogenic effect of N-nitroso-N-ethylurea in organ cultures of the kidneys of DBA/2 mice]. / Modifitsiruiushchee vliianie adenozilkobalamina na transplatsentarnyi kantserogennyi éffekt N-nitrozo-N-étilmocheviny v organnykh kul'turakh pochek myshei linii DBA/2.

Transplacental effect of cobalamin coenzyme, adenosylcobalamin (Adocbl), on the carcinogenic action of N-nitroso-N-ethylurea (ENU) was studied in culture of the mouse embryonic kidney tissue by histoautoradiography. Coenzyme methylmalonyl-CoA-mutase, Adocbl, injected into DBA/2 mice in the prenatal period did not stimulate the proliferative activity of epithelial cells of the embryonic kidney. The treatment with Adocbl did not intensify hyperplastic changes common for the early stages of carcinogenesis. The frequency of hyperplastic changes mainly of focal proliferation in kidney explants with the combined administration was considerably lower than with the isolated action of the carcinogen and amounted to 8.7% and 21.5%, respectively (P less than 0.001).

[Modifying effect of methylcobalamin in organ cultures of the mouse kidney when administered transplacentally in combination with N-nitrosoethylurea]. / Modifitsiruiushchee vliianie metilkobalamina v organnykh kul'turakh pochek myshei pri kombinirovannom transplatsentarnom deistvii s N-nitrozoétilmochevinoi.

The influence of methylcobalamin (MeCbl) on transplacental effect of N-nitrosoethylurea (NEU) was studied in organ cultures of embryonic tissue of DBA/2 mice by the histoautoradiography (3H TdR). A combined transplacental treatment of pregnant mice with MeCbl and NEU produced a 3.3-fold increase in the frequency of focal hyperplastic growth of epithelium as compared to the effect of NEU alone. Under such conditions the modifying effect of methylcobalamin, coenzyme of methionine synthetase, was probably due to an increase in the proliferative activity of epithelial cells.