Experiments on newborn rats demonstrated that hepatic monooxygenase system inductors, such as phenobarbital, benzonal, zixorin, increased their body weight, absolute and relative mass of newborn lungs when applied antenatally in contrast to dexamethasone which decreased the above parameters. The inductors increased pulmonary and hepatic phospholipid levels, which suggests that they are superior to dexamethasone in this respect.

The effect of thyroid hormones and the methylation inhibitor 5-azacytidine on the level of expression of thyroid hormone-responsive genes (malic enzyme and 6-phosphogluconate dehydrogenase genes) has been studied. DNA-RNA hybridization has shown there is an inverse correlation between the level of DNA methylation and gene expression of malic enzyme and 6-phosphogluconate dehydrogenase. Thus it suggests that the regulation of thyroid hormone gene expression can take place via DNA methylation blocking and that DNA demethylation is part of structural changes essential to the binding of thyroid hormones with DNA elements recognized by thyroid hormone receptors and to further induction of synthesis of specific mRNA.

Experiments with non-inbred mice established that there was a direct correlation between the defence index (DI) of monooxygenase enzyme (ME) inductors and the coefficient of variation of LD50 which were used to determine the DI of toxicants, which reflected the LD16-LD84 interval. This interval should be borne in mind while evaluating the effect of pharmacological agents exerting an inducing action of P-450-dependent hepatic monooxygenases, which allows the formula to be constructed.

Rat experiments have shown preliminary administration of phenobarbital and zixoryn (before ischemia) fails to prevent the hepatic monoxygenase system from ischemic lesion, followed by profound destructive changes in the liver, though the functional activity of the microsomal system remained high. Phenobarbital and zixoryn induction of monooxygenases in the postischemic period contributed to the complete restoration of the levels of microsomal cytochromes and the metabolic activity of xenobiotics in the liver just in its early periods. It is concluded that it is advisable to use the inductors in the postischemic restorative period to correct the detoxifying function of the liver.

Recombinant interferon treatment of donors' and bladder cancer patients' lymphocytes results in activation of natural killer cells which is in correlation with enhanced activity of 2,5-oligoadenylate synthetase in them. The study of sensitivity of bladder cancer cell primary cultures showed that the cells are sensitive to various interferons virtually in all the cases observed as indicated by high synthetase activity. The baseline level of 2,5-oligoadenylate synthetase in tumor cells surpassed that in natural killers from healthy donors which may be related to elevated levels of serum gamma-interferon in the above patients.

The metabolism in vitro of 4-androstene 3,17-dione--one of the steroid hormones--has been studied in liver microsomes of three species of bullhead: Cottocomephorus grewingki Dyb., Paracottus Kneri Dyb., Paracottus Kessleri Dyb. from Lake Baikal under norm and under induction of monooxygenases by 3-methylcholanthrene and arochlore 1254. The metabolism in vitro 4-androstene 3,17-dione in liver microsomes depends on fish sex, species and gonadal maturation. The rate of androstendione hydroxylation reliably decreases at monooxydase system induction of endoplasmic reticulum in bullhead liver before spawning and during spawning periods by 3-methylcholanthrene and arochlore 1254.

We examined the extrachromosomal DNA (exDNA, Hirt fraction) in ethidium bromide sensitive and resistant cells of line L929. The exDNA amount is greater in the latter. The amount of exDNA in L929 cells makes 0.19% of the total cellular DNA; the exDNA amounts in cells, resistant to 5 and 50 micrograms/ml ethidium bromide are 0.22 and 0.33%, resp. Using labelling by BudR, it is shown that approximately 16% exDNA in L cells constituted amplified sequences to be excreting to the culture medium. The Zn-independent endogenous nuclease is activated in the resistant cells. The treatment with cycloheximide (50 micrograms/ml) resulted in the increase in the exDNA amount and in the activation of Zn-independent endonuclease. The data obtained suggested that the activation of Zn-independent endonuclease may lead to the increase in the exDNA amount and determine presumably a high rate of cell adaptability to environmental conditions.

Using cultured A431 cells, a comparative analysis was performed of endocytosis stimulated by the epidermal growth factor (EGF) just following the ligand influence (early endocytosis) and after a 3 hour incubation of A431 cells with EGF (delay endocytosis). It is shown that at the early endocytosis the total amount of 125I-EGF, associated with cells, is decreased less than at the delay endocytosis. The decrease in total amount of cell-associated 125I-EGF was accompanied with the increase in the EGF concentration in the incubation medium. The data obtained suggested a lower rate of internalization for delay endocytosis. The Scatchard analysis of 125I-EGF-binding has shown that both high affinity EGF-receptor and low affinity EGF-receptor undergo the down-regulation. The Percoll gradient fractionation of EGF-loaded cells has shown that at the delay endocytosis 125I-EGF is displaced to the fraction of heavy endosomes and lysosomes slower than at the early endocytosis. It is suggested that a delay of EGF-receptor complexes transition from endosomes to lysosomes may arise during delay endocytosis.

Evidence is provided that selection of the Chinese hamster cells CHLV-79 RJK with ethidium bromide results in amplification and overexpression of mdr family genes, one of which is encoding a transmembrane P-glycoprotein reducing the intracellular drug concentration. It is likely that the amplified copies are located at or near the sites of resident mdr gene localization to look as an abnormal chromosomal banding pattern in chromosome 1q26. In the following selection steps to higher drug concentration, the cells are keeping the degree of amplification, but mdr gene expression increases by many times. The data suggest that the resistance of the Chinese hamster cells CHLV-79 RJK to higher concentrations of ethidium bromide may be achieved via a variety of mechanisms, including as well mdr gene amplification as transcriptional regulation of these genes.

In descendants of white rats with chronic alcoholic intoxication, the contents of DA in the brain and blood plasma, characteristics of GABA and opiate brain receptors, the contents of cAMP and other substances were studied as well as the c-fos gene expression. The data obtained suggest a considerable role of the changes in the DA system functions in the genesis of pathology in these descendants.

Male Wistar rats were inducted with phenobarbital and ziksorin. The inducing effect has been shown by hepatocyte hypertrophy involving the cytoplasm and nuclei. After phenobarbital injection cytoplasmic hypertrophy was due to redistribution of the plastic material in favour of the smooth-surface endoplasmic reticulum (SER). This redistribution occurred with the decrease of the energy forming and external synthetic functions of hepatocytes. After ziksorin injection SER hyperplasia was combined with proportional hyperplasia of the whole cytoplasmic organelles of the liver cells. This points to more optimal response of hepatocytes after ziksorin induction as compared with phenobarbital. Therefore, ziksorin can be recommended for clinical practice if it is necessary to stimulate processes of reparative regeneration in the liver.

The effect of different immunostimulants (prodigiosan, levamisole, T-activin, sodium diethyl dithiocarbamate, sodium nucleinate, lithium chloride, muramil dipeptide, B-activin) and mixed hepatic function oxidase inhibitors (cimetidine, chloramphenicol) or inducers (phenobarbital, flumecinol, rifampicin) on immune reactivity (macrophage function, humoral and cellular responses) and hepatic microsomal function (hexobarbital sleeping-time) was studied in non-inbred and BALB/c male mice. There was a high correlation between the ability of immunostimulants to depress hexobarbital metabolism and their ability to enhance macrophage activity (carbon clearance test), but not humoral and cellular immunity. No reciprocal changes occurred in immune reactivity after positive or negative pharmacological modulation of hepatic drug metabolizing enzyme activity.

The rat experiments studied the impact of inductors and inhibitors of enzymatic activity of xenobiotic metabolism on the pharmacological activity of sodium thiopental and ketamine and on the pharmacokinetics of sodium thiopental. Cocarboxylase, cobalt chloride and cimetidine enhanced the pharmacological action of sodium thiopental, but failed to exert any action on the effect of ketamine. The preparations of vitamin K, particularly vikasol and menadione sodium bisulfite, and phenobarbital attenuated the effects of these anesthetics, but tocopherol unchanged it. Phenobarbital and vikasol accelerated blood elimination of sodium thiopental, whereas cimetidine and cocarboxylase slowed down this process.

Intragastric CCl4 inhibited the activity of and lowered the levels of the major components of the hepatic monoohygenase enzyme system in one-month rats. Benzonal was found to be more effective in correcting the impaired monooxygenase enzyme system of hepatic cells in immature rats with acute hepatitis than silibor, phytin and zyxorin.

A fermentation medium balanced by the main components was developed for Cryptococcus diffluens strains producing penicillin-V-acylases (PA). It was shown that the culture needed for production of the enzyme was inductor, which was phenoxyacetic acid (POAA). Additional introduction of ethanol to the medium provided an increase in production of PA by 36 per cent and the culture growth by 25 per cent. Introduction of one of the following substances to the medium with POAA and ethanol i.e. (CN3COO)2Ca, FeSO4, proline or asparagine provided an additional increase in the production level of PA by 24 to 94 per cent. The use of the medium varieties will permit one to isolate highly productive cells of the culture.