[Transcobalamin II levels in blood plasma of children with acute leukemia]. / Soderzhanie transkobalamina II v plazme krovi u detei s ostrym leikozom.

Transcobalamin II (TcII) level was studied in plasma of 40 children with acute leukemia. TcII is a cobalamin-binding protein which mediated the cellular uptake of Cbl and interacted with surface membrane receptor of hemopoietic cells. Plasma TcII and cobalofilins were analysed by PAGE using 57Co-cyanocobalamin. In addition, the mature human placenta with high specificity and affinity to TcII receptors was applied for TcII plasma identification. As compared to control, significant difference of TcII activity in the plasma of children with ALL was noted. There were children with low and high TcII concentration vs. control (484 +/- 42 and 1166 +/- 62, p > 0.001). Therefore, it is necessary to assay individually all the biochemical parameters of Cbl-transport system of children with ALL for adequate metabolic correction.

[Synthesis of arachidonic acid cascade eicosanoids in tumors of various histogenesis in mice]. / Sintez éikozanoidov kaskada arakhidonovoi kisloty v opukholiakh raznogo gistogeneza u myshei.

The investigation was undertaken to characterize the profile of arachidonic acid metabolites in different spontaneous and transplantable tumors in mice. The five metabolites via the cyclooxygenase pathway (PGE2, PGF2 alpha, PGD2, TxB2, 6-keto-PGF1 alpha), as well as the three lipoxygenase products (5-HETE, 12-HETE, and 15-HETE) were monitored by thin layer chromatography and high performance liquid chromatography after "ex vivo" metabolism of exogenous [1-C14]-arachidonic acid by homogenates of tumor tissues. It was shown that all tumors had a unique profile of eicosanoids. The most cyclooxygenase activity along with the significant synthesis of PGE2, PGF2 alpha, and 6-keto-PGF1 alpha was noted in lung tumors. The antitumor effect of indomethacin was directly related to the ability of tumors to produce PGE2. On the other hand, there were varying lipoxygenase activities in tumors. In some cases, the extremely high levels of 15- and 12-HETE synthesis in neoplastic tissue could indicate that there was a basic possibility of using lipoxygenase inhibitors for suppressing malignant tumors.

[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).

[Active transport of cobalamins in leukemic cells of L-1210 mice]. / Aktivnyi transport kobalaminov v leikemicheskie kletki myshei L-1210.

The Tc-II receptors of cell surface membrane and the cobalamins entering into the L-1210 mouse leukemia cells were investigated. We used the blood serum Tc-II saturated with 57CoCNCbl for radioactivity determination separately in solubilized receptors and inside of the cells. The data on ligand regulation of the leukemic cell membrane receptors number were received. The internalization of radioactive complex of Tc-II and cobalamin was revealed during intensive 3H-thymidine incorporation into DNA of the cultivated cells.

[Quantitative evaluation of the surface membrane receptors of leukemic cells to blood serum transcobalamin-II]. / Kolichestvennaia otsenka retseptorov poverkhnostnoi membrany leikoznykh kletok k transkobalaminu-II syvorotki krovi.

Serum protein transcobalamin II (TC-II) is responsible for transport of cobalamins into mammalian cells. A method of quantitative estimation of plasma membrane receptors of hemopoietic cells to TC-II cobalamin complex is suggested. Analysis of mouse leukemia L1210 cells includes the saturation of radiolabelled ligand-receptor complex with papain. The number of receptors and 57CoCNCbl content in one cell is determined by differentiated radioactivity count of solubilized protein complexes and of cytoplasm.

[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).

[Nature of the modifying action of polyunsaturated fatty acids on the growth of transplantable tumors of different types]. / Kharakter modifitsiruiushchego deistvie polinenasyshchennykh zhirnykh kislot na rost perevivaemykh opukholei raznogo tipa.

Modification effect of sodium salts and ethers of linolenic, arachidonic and alpha-linolenic acids on the growth of transplantable mouse tumors was examined. Polyunsaturated fatty acids (PUFA) enhanced the growth of mammary adenocarcinoma Ca-755, whereas the opposite effect was observed in mice with leukemia L-1210 and sarcoma 180. No differences in the growth of melanoma B-16 and Lewis lung carcinoma were noted in control and experimental animals. Modification effect of PUFA was significantly suppressed by prostaglandin inhibitor indomethacin and to a lesser extent by antioxidant alpha-tocopherol.

[Kinetics of 57Co-cyanocobalamin distribution in the organs and tissues of mice with transplanted tumors]. / Kinetika raspredeleniia 57Co-tsianokobalamina v organakh i tkaniakh myshei s perevivaemymi opukholiami.

The distribution of cobalamin coenzyme precursor, 57Co-cyanocobalamin (57Co-CN-Cbl), in normal animals and in mammary adenocarcinoma (AC 755) and La leukemia-bearing mice has been studied during the exponential phase of tumour growth. The total uptake of radioactivity in the normal target organs was different. AC 755 took up 57Co-CN-Cbl selectively in all the periods of observation. In the case of La leukemia the highest rate of 57Co-CN-Cbl uptake in the spleen was found before its maximal hyperplasia. The accumulation of radioactivity in tumours led to a significant decrease in the total labelled cobalamin levels of the liver and kidneys. Analysis of the obtained kinetic curves revealed a different ability of AC 755 and leukemia cells for utilizing the pool of the endogenous cobalamin.

[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.

[Effect of methylcobalamin on methotrexate transport in normal and tumorous tissues]. / Vliianie metilkobalamina na transport metotreksata v normal'nye i opukholevye tkani.

The effect of methylcobalamin on 3H-methotrexate uptake by tumor and normal tissues of mice with mammary adenocarcinoma (Ca-755) was studied. Methylcobalamin stimulated the rate of 3H-methotrexate influx into the tumor and small intestine but did not change its influx into the spleen. The effect was dependent on the dose of methylcobalamin. Comparative analysis of the kinetic differences in 3H-methotrexate influx and efflux in tumor and susceptible host tissues revealed the optimal dose of methylcobalamin 0.01 mg/kg to improve the antitumor drug action.

[Methionine synthetase activity in tumor cells following administration of methylcobalamin and its analog]. / Aktivnost' metioninsintetazy v opukholevykh kletkakh pri vvedenii zhivotnym metilkobalamina i ego analoga.

Methylcobalamin (10 microgram/kg bw, intramuscularly, on the 3d and 5th days after tumor transplantation) or methylcobalamin chlorpalladat -- MeCbl.PdCl3 (250 mg/kg bw in 2% starch suspension per os on the 2d and 6th days) were given to C57BI mice bearing adenocarcinoma Ca--755. On the 8th day after transplantation the methionine synthetase activity and proliferative pool of tumor cells were estimated. It has been disclosed that under the effect of MeCbl the activity of methionine synthetase rises concurrently with an increase in pool of the proliferating cells. Inhibition of tumor growth (by 80--90%) after the treatment with MeCbl.PdCl3 correlated with a decrease in the holoenzyme level in tumor cells.