The influence of actinomycin D on the synthesis of extracellular ribonucleases by "Bacillus intermedius" (binase), B.pumilus (RNAse Bp) and B.amyloliquefaciens (barnase) was studied comparatively. When added during the active synthesis of the enzymes actinomycin D stimulated the biosynthesis of binase and RNAse Bp and had no influence on the barnase biosynthesis. The response of the bacillary RNAse biosynthesis to the added actinomycin D correlated with the differences in the nucleotide sequences of the genes encoding the enzymes. The Escherichia coli SURE recombinant strains carrying the plasmids with the genes of binase, RNAse Bp and barnase under different regulatory sequences, as well as the E.coli MC4100 recombinant strains carrying the plasmids with the beta-galactosidase gene under the promoters of the bacillary RNAse were isolated. However, the expression of the bacillary ribonuclease genes in the E.coli recombinant strains carrying the plasmids with the genes of the enzymes, as well as the expression of the beta-galactosidase gene from the promotors of the bacillary RNAses was not stimulated by actinomycin D irrespective of the dose and addition time.

Interaction between phosphorus amino acids analogs, 1-aminoalkylphosphonous and 1-aminoalkylthiophosphonic acids, and microsomes from the liver of phenobarbital-induced rabbits was studied. The phosphorus amino acids analogs cause type I and reverse type I spectral changes, respectively. A new reaction in the microsomal monooxygenase system was revealed. In the presence of NADPH, 1-aminoalkylphosphonous acids can be transformed to the corresponding 1-aminoalkylphosphonic acids by the reaction P-H-->P-OH. The reaction was monitored by 1H-NMR spectroscopy. 1-Aminoalkylphosphonous acids also serve as substrates for the NADPH-dependent monooxygenase system. 31P-NMR has shown that the oxidative desulfuration produces 1-aminoalkylphosphonous acids according to the reaction P=S-->P=O. Neither 1-aminoalkylphosphonous nor 1-aminoalkylphosphonic acids are deaminated in the NADPH-dependent monooxygenase system as follows from 1H-NMR spectroscopy.

Development of apoptosis was followed up in the cell line LIM-1863 of human colon carcinoma and in the same cell line with multiple drug resistance (MDR) related to the expression of gene mdr I and hyperproduction of protein P-glycoprotein 170 encoded by this gene. The number of cells with histological and ultrastructural features of apoptosis increased with acquirement by tumor cells of typical MDR. The enhancement of apoptosis in tumor cells with MDR results probably from the increase of cells with signs of terminal differentiation which is one of apoptosis inducers. Mitotic activity in both lines did not change essentially, but the original line had a more rapid growth than its analogue with MDR. Elimination of cells through apoptosis may be the cause of slower growth of the cell line with apoptosis. The rate of tumor growth depends on the balance between proliferative activity and apoptosis.

A low-molecular inductor of interferon-neovir-was found to increase the expression of estrogen and progesterone receptors in the uterus of ovariectomized rats weighing 210-230 g. It also gave more edge to progesterone receptors and reduced the receptor-reducing effect of tamoxifen in relatively young rats weighing 120-140 g. Sensitivity of breast tumor tissue to tamoxifen was restored and a 60-170 day-long period (observation time) of stabilization of the process ensued in 8 out of 10 patients, following administration of a total dose of 2,000 mg neovir (during one month) to patients with extensive breast tumors resistant to tamoxifen.

The effects of 2',5'-oligoadenilates (2,5A) on the survival of Wistar rats inoculated with Svec leukemia cells and the proliferation of tumoral cells were investigated. An agreement between the expression of c-myc protooncogene and inhibition of leukemic cell proliferation by 2,5A was found.

Administration of cobalt chloride (everyday dosage 50-100 mumol/kg) to rats in the course of pregnancy and first two days of postnatal period increases the activity of hemoxygenase + NADPH biliverdinreductase enzyme system in the brain of adult rats and induce this activity in new-born rats. Functional activity of serum albumin connected with bilirubin transport, the pH value in blood and bilirubin concentration in the brain of adult and new-born rats virtually do not change, whereas bilirubin concentration in the serum of pregnant rats received CoCl2 raises. When the same doses of cobalt chloride are administered to pregnant rats in combination with the mixture of high fatty acids and acetylsalicylic acid the activity of this enzyme system in the brain increases, functional activity of serum albumin connected with bilirubin transport decreases, bilirubin concentration in the brain raised (serum bilirubin concentration being comparatively low) at the same pH value in blood of both pregnant and new-born rats.

G11 mouse cells and SH2 rat cells transformed with simian adenovirus SA7 DNA showed inheritable oncogen-specific phenotypic normalization when treated with sense and antisense oligonucleotides complementary to long RNA sequences, plus or minus strands of the integrated adenovirus oncogenes E1A and E1B. Transitory treatment of the cells with the oligonucleotides in the absence of serum was shown to cause the appearance of normalized cell lines with fibroblastlike morphology, slower cell proliferation, and lack of ability to form colonies in soft agar. Proliferative activity and adhesion of the normalized cells that established cell lines were found to depend on the concentration of growth factors in the cultural medium. In some of the cell lines, an inhibition of transcription of the E1 oncogenes was observed. The normalization also produced cells that divided 2 - 5 times and died and cells that reverted to a transformed phenotype in 2 - 10 days. The latter appeared predominantly upon the action of the antisense oligonucleotides.

CCl4 given to Chinchilla rabbits aged 1 month caused impaired pharmacokinetics of cardiogrin, indicating suppression of absorptive and excretory functions of the liver in prepuberty. Silibor was found to produce no substantial restorative effects on hepatic absorptive and excretory functions in acute toxic hepatitis in the growing body. Phytin was shown to be not inferior to zyxorin and benzonal was superior to all the agents under study in activity.

Previously, the cDNA coding for human low-affinity receptor for IgE (FcERII/CD23) was cloned by three independent groups. Using oligonucleotide probes corresponding to the published cDNA sequence of CD23, we have isolated cDNA clones encoding FcERII from the cDNA library of B-lymphoblastoid cell line 1B obtained in our laboratory. Cloned nucleotide sequences of FcERII were shown to be identical to those from the RPMI8866 cell line. Using a DNA fragment containing the full-length cDNA copy of CD23 as a probe, CD23 expression in highly purified peripheral blood B lymphocytes was shown to be induced by recombinant human IL4 in a clearly dose-dependent manner.

Differential regulation of the expression of various families of the rat genome interspersed repetitive sequences by glucocorticoid hormones in liver has been demonstrated. Small ID-like RNA complementarily associated with high-molecular-weight cytoplasmic poly(A)-containing RNAs has been identified. The results obtained indicate that glucocorticoids hormones induce expression of the B2, ID, and L1 families in rat liver. The content of the transcripts of these repetitive elements is increased by the hormones in the molecules of heterogeneous nuclear RNA. In the molecules of high-molecular-mass poly(A)-containing cytoplasmic RNA glucocorticoids increase the content of the ID-homologous sequences. In the population of the small specific RNA the content of the ID-homologous transcripts is also increased. A suggestion is put forward about the involvement of the ID-like element in the hormonal posttranscriptional regulation of gene expression at the mRNA level.

Glucocorticoid responsive element (GRE) located -252 to -209 bp upstream of the transcription initiation site of mouse metallothionein I gene (mMT I) was identified in transient gene transfer experiments. This GRE, on its own, was capable of enhancing a reporter CAT gene expression in response to dexamethasone in orientation-independent manner when linked cis to a heterologous HSV TK gene promoter. The duplication of the GRE showed a synergistic effect on dexamethasone induction of the CAT gene. Nevertheless, the GRE located in its natural promoter region of mMT I gene (-330 to +70 bp) was found to provide low if any glucocorticoid induction of linked CAT gene, while showing strong cadmium regulation, comparable to the in vivo level.

The activity of benzopyrene hydroxylase (cytochrome P-450IA1) was studied in a mitogen-stimulated culture of peripheral blood lymphocytes from residents of the South Vietnam area treated with chlorophenoxy herbicides in the years of American aggression. The population residing in the untreated territory served as the control. The basal and induced benzopyrene hydroxylase activities, as well as the inducibility ratio were determined for each patient using the "lymphocytic test". The content of antipyrine metabolites and their percentage were estimated in the urine of the same patients using the antipyrine test. The computer processing of data allowed to perform primary analysis of the monooxygenase system in lymphocytes by groups in order to reveal correlations between the content of antipyrine metabolites in the urine and the cytochrome P-450IA1 in blood lymphocytes. The effect of residual amount of 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) on the human monooxygenase system is discussed.

Specific small ribonucleoprotein (alpha-RNP) complexes have been identified and characterized in the human epidermal carcinoma A-431 cells. The alpha-RNP complexes contain Alu-homologous small RNA, along with other small antisense RNA species. The epidermal growth factor (EGF) has been shown to induce selective specific changes in the expression of the small alpha-RNAs, the expression of the Alu-like RNA being repressed. Specific changes in the protein composition of the alpha-RNP complexes have been detected under the influence of EGF.

Stable mutant cells Cebr-1 and Cebr-2, resistant to ethidium bromide (EB) in concentration of 2 micrograms/ml, have been isolated by a multistep selection in Chinese hamster ovary cells. It was shown that Cebr-1 and Cebr-2 cells acquired a cross-resistance to unrelated drugs. Stable changes in the structure of chromosomes 1, 2, 5 and 8 were revealed by karyological analysis. Overexpression and amplification of mdr genes were detected in Cebr-2 cells using Northern RNA and Southern DNA blot hybridization. Two independent hybrids Hybr-1 and Hybr-2 were obtained by fusion of Cebr-2 cells with Chinese hamster lung V-79 RJK cells, sensitive to EB. Hybr-2 cells were characterized by the same level of EB-resistance as Cebr-2 cells. Hybr-1 cells have a lower level of EB-resistance than Cebr-2 cells. Hybr-2 cells have demonstrated amplification and overexpression of mdr gene, the same as in Cebr-2 cells, whereas in Hybr-1 cells no mdr gene amplification was observed, but the level of mdr gene expression was higher than in sensitive cells. The data suggest that resistance of Chinese hamster cells to EB is mediated by amplification and overexpression of mdr genes.