Arachidonic acid metabolism in growth control of A549 human lung adenocarcinoma cells.

The role of individual eicosanoids of the arachidonic acid (AA) cascade in the growth control of A549 human lung adenocarcinoma cells has been studied. Cyclooxygenase and lipoxygenase metabolites of [14C]AA incorporated were actively synthesized in the cultures of tumor cells with full confluence unaccomplished. In such cultures inhibitors of AA metabolism (indomethacin and esculetin) and also a lipoxygenase metabolite of AA, 15-hydroxyeicosatetraenoic acid (15-HETE), significantly suppressed the incorporation of [3H]thymidine and biosynthesis of prostaglandin E2 (PGE2). Other lipoxygenase metabolites of AA (5-HETE and 12-HETE) had no effect on these parameters. The basic fibroblast growth factor (bFGF) had practically no affect on the growth of A549 cells and the PGE2 production in cultures with 5% fetal calf serum (FCS); however, in the presence of 0.5% FCS this factor significantly increased the number of tumor cells. The growth-stimulating effect of bFGF was completely abolished by a cyclooxygenase inhibitor indomethacin. The data suggest a key role of PGE2 in the growth control of A549 cells with an active synthesis of cyclooxygenase and lipoxygenase metabolites of AA, its importance in realization of the mitogenic effect of bFGF, and specific features of 15-HETE as a down-regulator of the PGE2-dependent proliferation.

[The role of glycosaminoglycans and proteoglycans in hemopoiesis and the physiological functions of the blood cells]. / Rol' glikozaminoglikanov i proteoglikanov v gemopoéze i fiziologicheskikh funktsiiakh kletok krovi.

Literature review as well as own data on the role of glycosaminoglycans and proteoglycans of leukocytes, platelets and hemopoietic microenvironment are presented. These compounds are involved in the storage of lysosomal enzymes, cationic antibacterial polypeptides and other granular constituents of blood cells, take part in mediating of cellular interactions, occurring in hematopoiesis, phagocytosis, immunity and other processes. Due to the capacity to react with many substances, including enzymes, cell growth factors, cytokines, receptors, changing their conformation and biological activity glycosaminoglycans and proteoglycans can take part in regulation of cell adhesion, migration, proliferation differentiation and special functions of various types of hematopoietic and lymphoid cells.

[The use of verapamil in tests for determining the drug resistance of leukemic blasts]. / Ispol'zovanie verapamila v testakh dlia opredeleniia lekarstvennoi ustoichivosti leikoznykh blastov.

To determine prognostically unfavourable groups of acute leukemia patients, the authors studied the in vitro accumulation of 3H-vincristine (Vcr) and adriamycin (ADR) as well as inclusion of 3H-cytosar (Ara-C) into marrow blast DNA from patients showing different effects of treatment. It was found resistant to induction chemotherapy increases with verapamil addition to culture medium (Vrp+ cells). ADR inclusion into Vrp+ cells was the same as that into Vrp- cells. The inclusion of 3H-Ara-C into S-phase cell DNA in the cells Vrp+ was 3 time that in the cells Vrp-. All the responders to cytosar treatment had Vrp- blasts. It is evident that evaluation of Vrp effect on 3H-Vcr accumulation under short-term culturing is able to indicate groups of patients with low probability of achieving complete remissions in response to standard regimens of Vcr, Ara-C and anthracyclines treatment.

[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).

[Comparative evaluation of blast cell proliferation and effectiveness of combined chemotherapy in children with different immunocytological subvariants of acute lymphoblastic and nonlymphoblastic leukemia]. / Sravnitel'naia otsenka proliferatsii blastnykh kletok i éffektivnosti kombinirovannoi khimioterapii u detei s razlichnymi immunotsitologicheskimi subvariantami ostrogo limfoblastnogo i nelimfoblastnogo leikoza.

It has been found that kinetic parameters of proliferation in a dominating clone of bone marrow blast cells with Ia-positive and Ia-negative phenotype, as well as with expression of myeloid differentiating antigens (ICO-GM1 and ICO-G2), or in the absence of these antigens, do not significantly differ in children with subvariants MO-M4 of acute nonlymphoblastic leukemia, sensitive and resistant to the therapy. A higher rate of the bone marrow blast cell population growth and a lower effectiveness of the combined chemotherapy have been recorded in children with T-cell and pre-B-cell acute lymphoblastic leukemia as compared to acute lymphoblastic leukemia with the phenotype of blast cells that have only Ia-like or "common" antigens.

[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).

[Transplacental effect of methylcobalamine on the growth of embryonic mouse kidney tissue in organotypic cultivation]. / Transplatsentarnyi éffekt metilkobalamina na rost émbrional'noi tkani pochek myshei pri organotipicheskom kul'tivirovanii.

Transplacental growth-stimulating effect of the Cbl-coenzyme methylcobalamine (MeCbl) was revealed in organ cultures of embryonic kidney tissue in DBA/2 mice. MeCbl improved the survival of embryonic kidney explants and decreased the incidence of degenerative damage in cultures. The frequency of regeneration development was 30%. Hyperplastic epithelial changes were much more marked after transplacental MeCbl administration (71.8%), than in the control (9.0%).