Xenobiotics--inducers of benzo(a)pyrene hydroxylase (BPH)--exert different effects on mitogen-stimulated and mitogen-unstimulated human peripheral blood mononuclear cells (PBC). In mitogen-stimulated culture xenobiotics highly increase BPH activity and suppress cell blast transformation. The incubation of the unstimulated PBC in the presence of xenobiotics increases insignificantly BPH activity, intensifies T-cell differentiation and concanavalin A-induced proliferation. The BPH activity is mainly associated with the PBC adhered to plastic Petri dishes. However, the control and induced levels of BPH activity depend on the interaction between adhered and nonadhered cells.

A sharp decrease in the number of epidermal growth factor receptors (EGF-R) in the rat liver plasma membranes had been found at different stages of diethylnitrosamine-induced carcinogenesis. The complete loss of high-affinity binding sites for EGF did not prevent EGF-dependent autophosphorylation of EGF-R. Hepatocytes from the rat liver tumors in the primary culture had two classes of EGF-R: high and low affinity ones, though their number had been twice less than in the normal hepatocytes. The dynamics of internalization and down-regulation of EGF-R was very similar in the primary culture of transformed and normal hepatocytes. It testifies that there are some factors of microenvironment in the liver during carcinogenesis which cause the loss of EGF-R (down-regulation) and a decrease of their affinity (activation of protein kinase C). A possible autocrine or paracrine nature of these factors is discussed.

The data about the use of "antipyrine test" in clinical practice for studying the drug oxidation peculiarities are presented. The data characterize the main pharmacokinetic properties of antipyrine as a "metabolic marker" for quantitative estimation of the effects of inductors and inhibitors on the liver microsomal enzyme activity. The research methods are described and the data on the effects of different environmental factors on antipyrine metabolism are presented. The peculiarities of using the drug as a model for studying the effects of different environmental factors on the drug metabolism are formulated.

Rat embryonal fibroblasts of the second passage have been immortalized or transformed with the E1A region of the human adenovirus type 5 and the cloned c-Ha-ras oncogene. Several cell lines obtained greatly differ according to the criteria of the transformed phenotype: saturation cell density, the ability to be cloned on a substrate and in soft agar, the ability to give tumors in nude mice. We have transiently transfected these immortalized and transformed cell lines with CAT-plasmids containing the CAT gene under the control of promoters of the "cell-cycle dependent" genes (human hsp70 and protooncogene c-fos). The results showed that the expression of hsp-CAT and fos-CAT plasmids differed in great extent depending on whether the cells were immortalized (E1Aad5) or transformed (E1Aad5+Ha-ras). The role of cellular genes and cellular transcription factors influencing the expression of transiently transfected CAT-plasmids has been discussed.

The cytochrome P-450 isoforms have been studied in liver microsomes of some fish species from Lake Baikal. Using the inhibitory analysis of microsomal monooxygenase activities carried out by the specific polyclonal antibodies it has been shown that 3-methylcholanthrene, beta-naphthoflavone and arochlor 1254 induce isoforms immunologically related to cytochrome P-488c but not to the rat cytochrome P-450b in fish liver microsomes. The immunologic identity in isoforms of fish and rat cytochromes induced by methylcholanthrene has not been revealed. A possibility to use the method of the inhibitory analysis of fish microsomal activities by specific antibodies to the rat cytochrome P-450 isoforms for biomonitoring and biotesting of polycyclic hydrocarbons and polychlorinated biphenyls in aquatic systems is discussed.

Forty-six patients with acute viral hepatitis (AVH) varying in severity received standard therapy. Twenty of them were given an adjuvant 6-day course of benzonal. The activity of liver monooxygenase was evaluated before, after treatment (for 6-8 days) and at the height of the disease using antipyrine++ test. AVH was found to inhibit liver monooxygenase activity, this inhibition being on the increase with growing severity of the disease. Standard therapy failed to manage this condition, whereas the addition of benzonal lead to recovery of normal values of the antipyrine++ test. Benzonal-treated patients showed more rapid discontinuation of clinical and biochemical symptoms, their hospital stay was shorter. It is concluded that antipyrine++ test is an adequate criterion in the assessment of AVH gravity and in the prognosis of its course. An adjuvant treatment of AVH with benzonal promotes the recovery of monooxygenase system of hepatocytes resulting in disappearance of the clinical symptoms of the disease.

The effect of chlortetracycline on activity of the liver aryl amidases was studied. The antibiotic was used in a dose of 15 mg/kg for 6 days. It was noted that the use of chlortetracycline resulted in increased activity of the liver aryl amidases in young and old animals. In mature rabbits the aryl amidase activity under the experimental conditions lowered.

Intravenous injections to rabbits of perfluorocarbon emulsion containing perfluorodecaline (10 ml/kg, equivalent to 1.3 g of perfluorodecaline per 1 kg of body weight) produced a 2-4-fold increase of cytochrome P-450 content in the liver microsomes within 3-4 weeks. Cytochrome P-450 induction was followed by activation of the liver monoxygenase system evaluated by the rate of antipyrine excretion from the blood. On the 1st day after administration perfluorodecaline caused an insignificant (14%) inhibition of the monoxygenase system.

Mitochondrial RNA biosynthesis was studied at different time after hydrocortisone administration. Hydrocortisone induced liver mitochondrial RNA biosynthesis in vivo and in isolated organellae 15 min., 1.5 and 4 h after hormone injection. As shown by means of molecular hybridization of RNA-DNA, an increase in liver mitochondrial RNA biosynthesis induced by hydrocortisone administration was due to an increase in the expression of all mitochondrial genes simultaneously rather than to selective enhancement of individual gene transcription. Hydrocortisone changed the biosynthesis and transport of cytoplasmic RNA in the liver of intact rats. The incorporation of 3H-UTP into RNA by isolated liver mitochondria of control and hydrocortisone-treated rats was inhibited by ethidium bromide. RNA biosynthesis in isolated rat liver mitochondria was unchanged in 15-300 min. of 0.9% NaCl administration.

Gamma-aminobutyric acid (GABA) was shown to exert the immunodepressive effect. The use of GABA under induction of cytochrome P-450 of the liver by phenobarbital or rifampicin was not followed by immunodepression. The obtained data indicate the dependence of GABA pharmacological activity from the function of cytochrome P-450-dependent monooxygenase system of the liver.

The effect of an anticoagulant with the indirect action phepromaron on some parameters of the liver monooxygenase system (the activity of N-demethylase of amidopyrine, p-hydroxylase of aniline, levels of cytochromes P-450 and b5) was studied on rats receiving adequate nutrition. In the first hours of the investigation (at 3, 12, 24 hours) the intragastric administration of phepromaron in a dose of 10 mg/kg produced a decrease of p-hydroxylase activity, the levels of cytochrome P-450 and b5. At 72 hours the indices of the monooxygenase system significantly increased. Administration of phepromaron to animals receiving zyxorin (in a dose of 60 mg/kg per day for 3 days) failed to change the inducing effect of the drug on the activity of the liver monooxygenase system enzymes in all periods of the investigation.

TPP-Sn4+ was administered intraperitoneally (25 mg/kg body weight). The study was performed for 1-30 days. A day after administration the increase in the hemoprotein level 1.4 times was observed, as well as an increase in the level of p-hydroxylation of aniline. On 7-14 days the greatest increase in cytochrome P-450 content was observed. To clarity the mechanism of TPP-Sn4+ effect on cytochrome P-450, we studied its effect on the activity of heme oxygenase and LP rate. This compound is an inhibitor of heme oxygenase activity and reduces the rate of LP in the microsomes which regulates porphyrin metabolism in the organism.

Liver monoxygenase system function has been examined in psoriasis patients and possible modifications of current methods of therapy analyzed with due consideration for the detected disorders. A total of 139 patients with various clinical forms of psoriasis have been examined. The function of the liver monoxygenase system has been examined with the use of antipyrine test. The studies have revealed that this system's disorders are most marked in the patients with psoriatic eruptions involving a significant area, in whom the disease runs a protracted severe course. Twenty patients with normal and impaired functions of the monoxygenase system have been administered combined treatment including zixorin (600 mg orally once a week). The results evidence that zixorin improves the therapy efficacy, particularly in the patients with depressed activity of the liver microsomal enzymes. PUVA therapy has been administered to some patients. Zixorin has alleviated the side effects of phototherapy.