[Effect of exogenous and endogenous nitrosation factors on formation of N-nitrosodimethylamine in rats depending on the status of purine catabolism]. / Izuchenie vliianiia ékzogennykh i éndogennykh nitroziruiushchikh faktorov na obrazovanie N-nitrozodimetilamina u krys v zavisimosti ot sostoianiia purinovogo katabolizma.

Nitrogen dioxide's rats' inhalations with injections per os of pyrazole, amidopyrine and sodium nitrite lead to considerable increasing of endogenic N-nitrosodimethylamine formation, which had been determined by system gas chromatograph-thermal energetic analyser. This increasing essentially didn't depend on the rats' immunisation by vaccine BCG, which leads to the intensification of NO synthesis by peritoneal macrophages and others manifestations of their metabolic activation: increasing of creatine kinase and adenosine desaminase activities. It hadn't been brought to light the obvious dependent between changes of xanthine oxidase and xanthine dehydrogenase activities in the liver and blood serum and intensification of lipids peroxidation and also the amount of N-nitrosodimethylamine in the rats in the conditions of endogenic and exogenic nitrosation factors' influence.

The scientific platform and activity of the Ukrainian INEC Section.

The Ukrainian INEC Section is the most recently established chapter of the European Institute of Ecology and Cancer (INEC). We herewith review its organization and goals, membership, scientific platform, and areas of scientific activity.

Gaseous nitrogen dioxide increases the endogenous synthesis of carcinogenic N-nitrosodimethylamine in animals.

Inhalation of nitrogen dioxide (NO2) by mice administered orally amidopyrine (AP) and sodium nitrite resulted in increased biosynthesis of N-nitrosodimethylamine (NDMA), as determined by analysis using gas chromatography with thermal energy analyzer detector. These results were also confirmed indirectly in chronic experiments on rats using the system of biomarkers of NDMA formation (single-stranded DNA liver damages, alanine-aminotransferase, glutathione-S-transferase, and liver S9 fraction activity). The inhibition of NDMA metabolism by 4-methylpyrazol (4-MP) administration increases the sensitivity of NDMA biosynthesis assay in frozen whole-mouse powder. The results confirm that NO2 can serve as the precursor of nitrosamines.

Effect of N-nitrosoamines and nitrosationable pesticide tetramethylthiuram disulfide on soil microbiocenosis and potato yield: a model system.

The effect of carcinogenic N-nitrosoamines (NA), NA-producing tetramethylthiuram disulfide (TMTD) pesticide, and of various doses of nitrogen fertilizers (90, 180, and 270 kg/ha) on the forming and vital functions of microbiocenosis of light gray forest soil was studied. The quantity, nitrifying activity, and gas production of nitrifying bacteria increased under the influence of NA. The nitrosodimethylamine (NDMA) and the nitrosodibutilamine (NDBA) changed the correlation between the number of soil-inhabiting fungi and bacteria so that the former prevailed. The greatest effect was observed on the twentieth day of cultivation of the soil when high concentrations of NDMA (50 mcg/kg) and NDBA (105 mcg/kg) were used. The typical dominant species among the fungi was the phytotoxigenic Penicillium funiculosum. The nitrosationable pesticide tetramethylthiuram disulfide (TMTD) applied with nitrogen fertilizers in a dose of 180 and 270 kg/ha exerted an influence on the microbiocenosis of the soil similar to NA. The potato yield decreased and the ecology of microbiocenosis deteriorated under these conditions in a model vegetable experiment. It is suggested that the nitrosoamines and their precursors may change the balance of nitrogen, decrease the yield of plants, and deteriorate the ecological balance.

Ecological aspects in cancer education.

Some aspects of modern ecology should be included in any graduate teaching program on preventive oncology and medicine. In the study of environmental carcinogenesis, the influence of carcinogenic agents on natural ecosystems and living organisms, integral ecological monitoring, naturally occurring carcinogens, and evaluation of complex risk assessment of the environment deserve particular attention. It is also important to integrate biochemical and molecular markers into epidemiology studies in order to correctly evaluate and prevent the cancer risk to humans that results from environmental factors.

New approaches to ecological oncology.

A definition of ecological oncology is given and its subject is discussed. Primary attention is paid to insufficiently studied aspects of this novel scientific discipline: the influence of carcinogens on the natural biocenoses and their role in the evolutional processes, the transformation of carcinogens by living organisms, and the ecological monitoring of environmental carcinogenic substances.

The carcinogenic danger of nitrie pollution of the environment.

Presented are the literature data as well as the results of our own investigations on the genotoxic and carcinogenic effects of sodium nitrite (SN). The carcinogenicity of SN detected in animal experiments appears to be related to the formation of nitroso compounds from endogenous nitrosable precursors. Sodium nitrite possesses transforming and promoting effects in cell cultures, as well as mutagenic effects in the bacterial systems, where the predominant effect of SN was compared to that of N-nitrosodimethylamine (NDMA). Prolonged pretreatment with SN amplifies the liver DNA damage in rats in case of NDMA endogenous synthesis.

[The role of nitrites in carcinogenesis]. / Rol' nitritov v kantserogeneze.

Data from literature as well as the results of the author's investigations on the genotoxic and carcinogenic effects of sodium nitrite (SN) are presented. Carcinogenicity of SN detected in animal experiments proved to be connected with the formation of nitroso compounds from endogenous nitrosable precursors. Sodium nitrite possessed the transforming and promoting effects in the cell cultures as well as the mutagenic effects in the bacterial systems where predominant effect of SN as compared with N-nitrosodimethylamine (NDMA) was registered. The prolonged pretreatment with SN amplified the liver DNA damage in rats in case of NDMA endogenous synthesis.

[Characteristics of action of precursors of carcinogenic nitroso-compounds on cell cultures]. / Osobennosti deistviia predshestvennikov kantserogennykh nitrozosoedinenii na kletochnye kul'tury.

On the primary rat lung cell cultures, a study was made of the transforming action of sodium nitrite (NN) and amidopyrine combination with the control for formation of carcinogen--N-nitrosodimethylamine (NDMA) in growth medium. The manifestation of transformation was registered by appearance of morphological changes and multilayer growth foci. As criteria for evaluation after 48 hour treatments with NDMA, NN and AP, were used DNA-synthetizing activity of cells, mitotic index, frequency of mitoses pathology, monolayer density. The effects of transforming dose of NN alone and in combination with AP were the same. But malignization (tumor development in newborn rats in the points of cell suspension inoculation) took place only after administration of NN in combination with AP, when carcinogen was formed. Theophylline decreased the action of NN-AP combination.

[Tumor development and monooxygenase activity in the liver of mice exposed to the combined action of N-nitrosodimethylamine and benz(a)pyrene]. / Razvitie opukholei i aktivnost' monooksigenaz pecheni u myshei pri kombinirovannom deistvii N-nitrozodimetilamina i benz(a)pirena.

The combined administration to mice of N-nitrosodimethylamine (NDMA) in drinking water and of benz(a)pyrene (BP) in skin applications induces mainly skin tumours and the use of BP in food--stomach tumours. The skin application of BP prevents the development of tumours after NDMA administration. The combined action of these carcinogens reduces the latent period of tumour incidence, lowers the induction of BP-hydroxylase and the activity of N-demethylase of NDMA.

[Effect of vitamin A on the endogenous synthesis and system of N-nitrosodimethylamine detoxication in the rat liver]. / Vliianie vitamina A na éndogennyi sintez i sistemu detoksikatsii N-nitrozodimetilamina v pecheni krys.

The administration of N-nitrosodimethylamine (NDMA) and its endogenic synthesis from amidopyrine and sodium nitrite decreases in the liver the level of reduced glutathione, ascorbic acid, glutathione reductase and glutathione-S-transferase activities, the accumulation of oxidized glutathione as well as the damage of DNA. The gamma-glutamyltransferase activity, the marker of carcinogenesis, increased. The damaging action of NDMA under the influence of vitamin A deficiency increased, but the vitamin excess decreased the biochemical changes in the liver.

[DNA alkylation during endogenous synthesis of N-nitrosodimethylamine]. / Alkilirovanie DNK pri éndogennom sinteze N-nitrozodimetilamina.

The simultaneous administration of 14C-dimethylamine and sodium nitrite to rat stomach produces the formation of O6-methylguanine and 7-methylguanine in the liver DNA as a result of the endogenic synthesis of N-nitrosodimethylamine (NDMA). Methylation of DNA was also observed in the rat kidney and lung. Alkylation of O6-position of guanine and removal of its methylated product from the DNA occurred in the liver to a greater extent than in the other NDMA target organs. Pretreatment of rats with sodium nitrite increased the alkylation of liver DNA caused by endogenic synthesis of NDMA. The formation of alkylated products in DNA may be used as a marker for the endogenic formation of NDMA from precursors.

[Approaches to ecological monitoring of chemical carcinogens]. / Podkhody k ékologicheskomu monitoringu khimicheskikh kantserogenov.

The approaches to ecological monitoring of carcinogens including the principles of its organization as well as the choice of the animals and plants as nature monitors are discussed. The classification of integral monitoring of carcinogens including bioecological (natural), sanitary-hygienic and medicobiological monitoring is proposed.

[Effect of N-nitrosodimethylamine and precursors of this carcinogen on rat kidney cells in monolayer culture]. / Deistvie N-nitrozodimetilamina i predshestvennikov étogo kantserogena na kletki pochek krys v odnosloinoi kul'ture.

Kidney tissue culture of 3-day old rats was cultivated in the presence of carcinogenic N-nitrosodimethylamine (NDMA), sodium nitrite, amidopyrine and a combination of these substances forming NDMA. All these substances induce changes in the number of DNA-synthesizing cells, monolayer density, percentage ratio of epithelial and fibroblastoid cells in the kidney cultures. The above changes are typical of each of the tested components, that permits using one-layer culture of the rat kidneys as a model for investigating cell response to the precursors of NDMA and to this carcinogen.

[Carcinogenic activity of some Soviet drug preparations]. / Izuchenie kantserogennoi aktivnosti u nekotorykh otechestvennykh lekarstvennykh preparatov.

After the long-term administration of doxilane-diolane, cresacin, antioxidant S-1 and fluorine varnish to mongrel albino rats and mice no difference in the level of spontaneous tumours both in the control and experimental groups of animals was observed. It is concluded that these drugs possess no carcinogenic activity.

[Transplacental effect of sodium nitrite on rat lung cells with their subsequent culture in the medium with precursors of N-nitrosodimethylamine]. / Transplatsentarnoe deistvie nitrita natriia na kletki legkikh krys s posleduiushchim kul'tivirovaniem v srede s predshestvennikami N-nitrozodimetilamina.

Mongrel rats of 12th day of pregnancy were administered sodium nitrite, amidopyrine, mixture of these substances and N-nitrosodimethylamine (NDMA) as well as alpha-tocopherol + ascorbic acid with drinking water. The cultivated lung cells of 3-day newborn rats with NDMA and its precursors were incubated. The transplacental effect of sodium nitrite on rat lung cells was observed. It was manifested in a decrease of the cell suspension viability, in an increase of the pathological mitosis level as well as in changes in cell responses to NDMA. The combination of sodium nitrite with phenobarbital considerably increased sensitivity of cells to the effect of NDMA, mixture of sodium nitrite with amidopyrine and amidopyrine.