A study was made of the expression of the cellular oncogens c--myc, c--sis and c--abl in mononuclears from normal donors and patients with different patterns of leukemia and hemopoietic dysplasia using spot hybridization on nitrocellulose filters with virus homologs of the given oncogens. Altogether 43 persons were examined. No specific expression of the oncogens indicated was established whatever the pattern of leukemia. The relationship between the expression of these oncogens and the efficacy of the treatment of acute myeloblastic leukemia was demonstrated. However, in the given investigations, no differences were identified in the expression of oncogens in the leukemic and normal cells stimulated with PHA and phorbolic ether. Enhanced expression of cellular oncogens myc, sis and abl occurred in acute leukemia.

Random bred male rats were given drinking water with phenobarbital (PB) (daily doses 0.4; 2 and 10 mg/kg) during 120 days. Activity of mixed function of oxygenases (content of cytochromes P-450) were enhanced after PB treatment in doses 2 and 10 mg/kg. Following PB treatment the animals were injected 5-times ethyleneimine derivate--fotrin at the doses 2, 4 and 7 mg/kg. The induction of mixed function of oxygenases resulted in significant decrease in the number of cells with chromosome aberrations.

The effect of interferon inductors i.e. double stranded RNAs from S. cerevisiae and phage F6 on the liver detoxicating function was studied on noninbred albino mice. The liver detoxicating function was tested by duration of hexenal sleep. It was shown that intraperitoneal administration of the yeast and phage RNAs in doses of 1/5 LD50 for three times led to increasing of the narcotic sleep duration in the animals by 65 and 207 per cent, respectively. The effect was of the dose-dependent nature. The doses not inducing reliable inhibition of hexenal metabolism were equal to 1/10 LD50 for the yeast dsRNA and 1/27 LD50 for the phage dsRNA. The inhibitory effect of the dsRNAs was retained for 2-3 days after discontinuation of the drug use. When the dsRNAs were administered simultaneously with nembutal, an inductor of the liver microsomal enzymes, the dsRNAs eliminated its inducing effect. Simultaneous administration of alpha-tocopherol lowered the dsRNA effect on hexenal metabolism. The findings suggested that the dsRNA inhibitory effect on the liver detoxicating function was grounded on the mechanisms associated with inhibition of syntheses and activation of lipid peroxidation specific of the monooxygenase system under the action of the dsRNAs.

Pretreatment of Wistar male rats with disulfiram (DSF, 500 mg/kg, three times, orally) or butylhydroxyanisole (BHA, 400 mg/kg, three times, orally) was shown to protect animals completely against intoxication with diethylnitrosamine (DENA) in the dose equal to LD50 (280 mg/kg, once, orally). DSF and BHA were also found to produce a significant modification of the 2nd stage of metabolism of xenobiotics: to induce the activity of cytosol and microsomal glutathione-S-transferases (GST) (by 1.7 and 2 times, 2.3 and 3.1 times, respectively), the content of glutathione (by 1.6 and 2.3 times), the activity of UDP glucuronosyltransferase (UDP-GT) (by 2 and 3.2 times) but to decrease the activity of sulfotransferase (by 22 and 35%). Administration of DENA decreased the activity of GST, UDP-GT and the content of glutathione, however they remain significantly higher than the corresponding parameters in intact animals. It is concluded that the protective action of DSF and BHA is related greatly to the induction of the systems of conjugation with glutathione and UDP-glucuronic acid.

Calcium pantothenate (CaP), calcium 4'-phosphopantothenate (CaPP), pantethine, panthenol, sulfopantetheine and CoA decrease acute toxicity of acetaldehyde in mice. All studied compounds diminish duration of the narcotic action of ethanol--ET (3.5 g/kg intraperitoneally) in mice and rats. In the latter this effect is realized at the expense of "long sleeping" and "middle sleeping" animals. CaP (150 mg/kg subcutaneously) and CaPP (100 mg/kg subcutaneously) prevent hypothermia and a decrease of oxygen consumption in rats induced by ET administration. Combined administration of ET, CaP and CaPP leads to a characteristic increase of acid-soluble CoA fractions in the rat liver and a relative decrease of acetyl CoA synthetase and N-acetyltransferase reactions. The antitoxic effect of preparations of pantothenic acid is not mediated by CoA-dependent reactions of detoxication, but most probably is due to intensification of ET oxidation and perhaps to its elimination from the organism.

Two polyadenylated transcripts of the jockey are detected at different stages of Drosophila melanogaster ontogenesis and in the cell culture. They have the same length as complete and deleted copies of jockey and correspond to the DNA strand containing open reading frames coding for polypeptides which are homologous to retroviral RNA-(DNA)-binding proteins and to their reverse transcriptases. The results of the experiments, where transcription was inhibited with alpha-amanitin in vivo, indicate that jockey is transcribed by RNA polymerase II. The analysis of expression of CAT constructions made on the basis of jockey, and the detection of a fixed site for transcription initiation in jockey genomic and transfected copies have shown that jockey transcription is controlled by an internal promoter located not farther than 12 nucleotides from the beginning of the element. Such an inward location of the promoter allows it to be preserved in replication via reverse transcription and accounts for the distribution of jockey and probably other LINEs throughout the genome. This is the case of the first internal promoter described for RNA polymerase II. The comparison of starting sequences of LINEs in Drosophila makes it possible to detect core sequences of such a promoter.

The effect of chemically inert perfluorodecalin (PFD) on the development of hypersensitive reactions of immediate and delayed types in guinea pigs and mice was studied. It was found that administration of PFD to animals both before sensitization (mice) and during the development of sensitization (guinea pigs) reduced the degree of the both types of hypersensitivity.

Differentiated human B-cells of the IgG+ sublines obtained as a result of switching from IgM to IgG synthesis in the 6410t line and its IgM+ lines gradually reduce the level of IgM secretion after the inductor removal. IgG synthesis can be partially or fully recovered by treating the IgG+ sublines with a polyclonal activator of B-lymphocytes, lipopolysaccharide W from Gram negative bacteria. In the conditions of certain regulatory effects, differentiated IgG+ cells are capable to pass reversibly in the state of functional rest and synthesis initiation.

The receptor cycle of the steroidal hormones since the moment of the hormone penetration into the cell until the hormone-receptor complex destruction was considered. The interaction of the steroid with the cytoplasmic membrane of the target cell is the primary link in the hormonal effect implementation. The steroidal regulation of matrix activity of the genome is mediated by intracellular receptors of the steroids located in the cytoplasm of the target cell. Sites of specific binding of the steroids were found also on the membranes of mitochondria, lysosomes, endoplasmic reticulum. The effect of the steroids on the functioning of these subcellular organelles is extragenomic. The interaction of the steroidal molecule with different receptors triggers the cascade of the biochemical reactions determining the tissue response to the hormonal signal.

The induction of immunoglobulin heavy chain classes switch from IgM to IgG was demonstrated in vitro in cells of RPMI-6410t line. The IgG+-sublines, formed as a result of the switch are characterized by instability of IgG synthesis. After removal of the inductor from the growth environment, IgG+ cells gradually reduce the level of secreted IgG. Such a transition to the functional rest state is likely to be connected with the convertible Ig-gene activity suppression in IgG+ cells, since after their activation by LPS IgG-secretion is partly or completely restored. The IgG+-sublines obtained may serve a convenient model for investigating the Ig-gene expression regulation in differentiated human B-cells.

G-banded metaphase chromosomes of Chinese hamster V-79 RJK cells resistant to ethidium bromide (2.5 and 10 mcg/ml) have been analysed. The cells of the first selection step (clone IVerb-2, the 9th passage) revealed definite karyotypical instabilities. Amplifications or, in rare cases, deletions were found in chromosomes Z1 and Z6 which appear to have derived from chromosome 1. The amplified region in chromosome Z6 varied considerably in morphology. The chromosome instability, detected in Z1 and Z6, was reproducible in cells throughout the eight independent clones isolated from clone IVebr-2 under non-selective conditions. The data obtained allow to suggest a genetically conditioned mechanism of the above chromosome instability. In the population of resistant cells on the second step of selection (clone I Vebr-5, the 9th passage) the frequency of the cells with amplification increased up to 100%. The length of amplifications increased in the majority of cells. In the cells of the third step of selection (clone IVerb-10, the 12th passage) with near-tetraploid chromosome composition, besides amplifications some specific rearrangements of chromosomes 2 and 7 (markers Z16, Z17) were revealed. The above rearrangements are indicative of the karyotypical destabilization in the drug resistant cells, and may be evaluated as secondary phenomena casually connected with amplifications found at the earlier steps of selection.

Vitamin B1 in rats induced in the liver elevation of activity of metabolic enzymes of xenobiotics bound with membranes (dimethylaniline N-demethylase, aniline n-hydroxylase, aryl esterase). At the same time activity of the cytoplasmatic enzymes alcohol dehydrogenase and glutathione-S-transferase was appreciably lowered. An additional load with thiamine (20 mg/kg) led to a drop in activity of the membrane-bound enzymes. Vitamin B1 deficiency modified the effect of the inductor phenobarbital. Additional administration of vitamin B1 to thiamine-deficient animals normalized the thiamine level in the liver, and activity of hydroxylase, aryl esterase, formaldehyde dehydrogenase, and significantly decreased demethylase activity. In vitamin B1-deficient animals high detergent concentrations significantly suppressed NADH-dichlorophenol-indophenol-reductase activity, while low concentrations activated this enzyme as compared to the control.

The content of cytochrome P-450 has been measured in primary hepatomas induced by diethylnitrosamine. As a rule, the enzyme content in hepatomas was decreased, as compared to normal liver and tumor-affected liver, but some hepatomas contained cytochrome P-450 in greater amount than normal tissue. Aroclor 1254 induced an increase in cytochrome P-450 content, which was identical in hepatomas, normal liver and tumor-affected liver. The dependence of hepatoma morphology on cytochrome P-450 content was not detected.

Relation between induced mutations of plasmid pAP18-1 (Tc, Col) and alterations in it's restriction map was studied. Nitrosoguanidine induced mutations of transfer regulation system and incompatibility of this plasmid related with alteration in the situation of recognition sites for restrictases EcoR1 and Sal1 in map positions 42.2-4.3 and 12.9-17.9 MD. Insertions of transposons Tn5 and Tn9 into the plasmid DNA resulted in a decrease of incompatibility level.

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.

Lethal and mutagenic effects of N-nitrosomethyl biuret on the organism producing a complex of proteolytic enzymes i. e. Acremonium chrysogenum were studied. It was shown that methionine inhibited production of the protease complex in the induced prototrophic mutants. The selected mutants were classified according to the level of enzyme biosynthesis induction by methionine.