A constant fine regulation of gene expression is needed for the normal development to proceed and for the physiological homeostasis to be maintained. In many cases such a regulation in eukaryotes is realized at the level of transcription, involving various cis- and trans-regulatory genomic elements. The review provides the data on the structure of elements determining the level of gene transcription in response to the action of various environmental factors and effectors, responsible for coordinated expression of the genes which provide for tissue-specific transcription and self-regulation of gene transcription. The data were considered on regulation of gene activity by mobile genetic elements and a relationship between the mechanisms of regulation of gene expression and evolution has been formulated.

The modern data on Escherichia coli K-12 ilv genes expression are reviewed. The problems of regulation of the ilv genes activity and of their possible role in the process of cell adaptation to changeable environment are discussed.

Using monospecific immune antiserum the expression of beta-lactamase bacterial gene (from the plasmid pBR322) in transformed TK+ Chinese hamster cells was studied. It is shown that in some TK+-clones the beta-lactamase gene is expressed and this expression is stimulated by an inhibitor of DNA methylation-5-azacytidine. Two physically linked genes (the Herpes simplex thymidine kinase gene, and the beta-lactamase gene) introduced into the Chinese hamster cells on the same plasmid are found to be expressed independently.

It has been shown in rat experiments that administration of zixoryn brings about an increase in the liver weight and the content of cytochromes P-450 and b5, and activates the aniline-hydroxylase reaction. The induction activity pattern of zixoryn is similar to that of phenobarbital-type inducers. However, it is inferior to phenobarbital in the degree of activity and causes an atypically dramatic increment of the content of cytochrome b5. It is assumed that the mechanism of zixoryn action is linked with acceleration of the synthesis of microsomal oxidation enzymes and stabilization of cytochrome P-450 in a catalytically active state.

The transfer of Morris hepatoma cells induced by the hormone within 10-60 min in to a hormone-free medium is associated with the augmentation of tyrosine aminotransferase synthesis. The kinetics of this process does not differ from that of the hormone-induced enzyme. The return of tyrosine aminotransferase synthesis to the basal level occurs 15-20 hours after the hormone withdrawal from the medium, although the concentration of the intranuclear hormone sharply decreases already after 3 hours. It was demonstrated that the presence in the hepatoma cell nuclei of 20-25% of the initially bound hormone for at least 20 hours after the cell transfer to the hormone-free medium is not sufficient for maintaining a high level of tyrosine aminotransferase gene expression. Using two-dimensional electrophoresis of 3H-labeled hepatoma cell proteins, it was demonstrated that the observed high activity of tyrosine aminotransferase is due to the de novo synthesis of enzyme molecules rather than to the existence of preformed long-living tyrosine aminotransferase molecules inside the cell. Study of [14C]uridine incorporation into non-ribosomal nuclear RNA of hepatoma cells showed a long-term presence of the label in the RNA throughout the chase experiment. It was assumed that the high activity of the enzyme for 10-15 hours after the hormone release from the hepatoma cell nuclei is due to the accumulation in the nuclei of long-living pre-mRNA molecules synthesized after the hormone addition to the cells and during the first hours after the cell transfer to the hormone-free medium.(ABSTRACT TRUNCATED AT 250 WORDS)

Induction of the monooxygenase system of xenobiotic metabolism by means of hexachlorobenzene (HCB) was studied in rat liver microsomes as compared with induction using phenobarbital (PB) and 3-methylcholanthrene (3-MC). HCB was shown to increase the content of cytochrome P-450 as well as aminopyrine- and benzphetamine-N-demethylase activities in liver microsomes. At the same time, HCB increased the benzpyrene hydroxylase activity as it was the case in induction with 3-MC. Electrophoresis in SDS-polyacrylamide gel showed that HCB, as phenobarbital does, induced appearance of the protein with a molecular mass 52,000 (cytochrome P-450) but not of the protein of molecular mass 56,000, which is the main isozyme of cytochrome P-450 in 3-MC microsomes (P-448). Except of cytochrome P-450, cytochrome, immunologically similar to cytochrome-P-448 from 3-MC microsomes, constituted 10% of the total content of cytochrome in HCB microsomes as shown by rocket immunoelectrophoresis using monospecific antibodies towards individual cytochromes P-448 and P-450 (anti-P-448 and anti-P-450). Anti-P-450 and especially anti-P-448 inhibited benzpyrene hydroxylase in HCB microsomes. HCB appears to be an inductor of a "mixed" type.

Chromatography on 1.8-diaminooctyl-Sepharose and DEAE-Sephacel resulted in 4 fractions of cytochrome P-450 from liver microsomes of 3-methylcholanthrene-induced Wistar rats. All the four fractions differed in terms of their absorption maxima in the CO-reduced state, Mr and catalytic activity. Only one cytochrome fraction (cytochrome P-450 C) possessed a high activity upon benz(a)pyrene hydroxylation. All cytochrome P-450 forms were characterized by a low rate of aminopyrine N-demethylation. Antibodies against cytochrome P-450 C (P-448) (anti-P-448) were raised. Cytochromes of fractions A, B1 and B2 in the Ouchterlony reaction of double immunodiffusion did not give precipitation bands with anti-P-448. Neither of the four cytochrome P-450 forms interacted with the antibodies raised against cytochrome P-450 isolated from liver microsomes of rats induced with phenobarbital. The procedure developed is applicable to the isolation of multiple forms of cytochrome P-450 from liver microsomes of 3-methylcholanthrene-induced rats. Using rocket immunoelectrophoresis, cytochrome P-450 C possessing a high (as compared to benz(a)pyrene metabolism) activity (18 nmol/min/nmol cytochrome) and a high (60-70%) content in 3-methylcholanthrene-induced rat liver microsomes was shown to give a relatively high yield.

Cytochrome P-450 PB localization in the livers of embryos, pregnant, non-pregnant female, and male Wistar rats was investigated immunomorphologically after phenobarbital (PB) treatment. The highest level of cytochrome P-450 PB induction was observed in the livers of male rats where the antigen invaded almost the whole liver lobule. About half of the cells within the lobule of non-pregnant female rat livers were stained and were located around the central vein area. Pregnant females had two times less indication than the non-pregnant group and only a quarter of the cells in the lobule of the liver adjacent to the central vein were stained for P-450 PB. The indication of cytochrome P-450 PB was absent from 17-18-day-old embryonal livers which were subjected to the transplacental action of the inducer. Only in one case out of seven were small groups of cells and single cells in the embryonal liver stained positively for cytochrome P-450 PB. It is obvious that during pregnancy, the mother's body exerts a significant influence on the detoxifying function of the fetal liver.

Content of cytochromes P-450 was lower in liver tissue of NZB mice strain as compared with the NZW strain. Lipid peroxidation in microsomal fraction was higher in females as compared with males (P less than 0.05); it was also higher in females of the NZB mice strain than in the NZW strain (P less than 0.05).

The enzymatic methylation of specific cytosine residues in DNA plays a part in controlling gene expression. Low methylation levels may be a necessary condition for gene expression. The chemical carcinogens exert their effect on the enzymatic methylation of mammalian DNA and can cause hypomethylation. Demethylated sites do not become remethylated in the subsequent cell cycles. The consequence of DNA hypomethylation may be both stimulation of cell differentiation and initiation of carcinogenesis.

The data are provided on benzonal as having the properties of the monoxygenase system inducer, evidenced by the shortening of hexenal sleep, increase of the intensity of the epr-signal of cytochrome P-450, activation of lipid peroxidation, carboxylesterase and arylesterase in the liver. The properties of benzonal described can be made use of for increasing the body resistance to the toxic action of xenobiotics.

The metabolic activation of benz(a)pyrene (BP) catalyzed by rat liver microsomes and isolated liver nuclei in the presence of certain inhibitors of the monooxygenase system was studied. Several forms of cytochrome P-450 are supposed to participate in metabolic conversion of BP. The specificity of cytochrome P-450 isoforms contained in the endoplasmic reticulum and in nuclear membranes is discussed.

The content of cytochrome P450 and monooxygenase activity has been studied in the liver of Baikal fishes (Coregonus automnalis, Thymallus articus, Brachymystax lenok and Cottocomphorus greminsky). The administration of 3-methylcholanthrene increases considerably the level of metabolic activity of microsomal fraction and cytochrome P450 content in liver. The data of microsomal fractions of rats and fishes liver electrophoresis have shown that xenobiotic causes the synthesis of similar according to the molecular weight forms of cytochrome P450 in these animals. The induction of microsomal monooxygenase inhibits the lipid peroxidation of microsomal fraction.