It is stated that phenobarbital used as the most potent inductor of the monoxygenase enzymic system of the liver in different pathologies has substantial side effects. In this connection the search of active inductive agents devoid of phenobarbital deficiencies is an important issue. Zixorene, a Hungarian drug developed to solve the problem, is weak as an inductor and has deficiencies of its own. A fitting substitute for phenobarbital is benzonal which is not inferior to phenobarbital in inductive activity but lacks its drawbacks. It is used both as a hypobilirubinemic agent and a drug restoring a disordered monohygenase system of the liver in different pathologies. Benhonal is metabolized in the gastrointestinal tract and the liver generating an active metabolite of phenobarbital. It is suggested that slow formation of phenobarbital in small quantities determines its more optimal interaction with the corresponding hepatic receptors resulting in the appearance of a marked inductive action while side effects are significantly decreased.

A study was made of the effect of zixorin, an inductor of liver cytochrome P-450, on the intensity of the immediate type allergic reaction--active food anaphylaxis in response to ovalbumin in guinea-pigs. Intraperitoneal injection of zixorin in a dose of 50 mg/kh for 3 days before administration of the antigen resolution dose was found to lower 2,3-fold the level of lethal outcomes due to the anaphylactic shock. It is suggested that zixorin may be used in multimodality treatment of food allergy.

It has been shown that inhibition of Bacillus subtilis alpha-amylase formation by the level of the active enzyme in the cultural medium leads to the decrease of translation accompanied by reduction of level of [14C] valin transport into the cells.

With help of nitrosoguanidine 60 mutants of F-like plasmids pAP18-1 drd::Tn 5 and pAP18-1::Tn 9 were induced which determined resistance of E. coli cells of specific phage MS2. Mutational changes in fin-locus of those plasmids were accompanied by phenotypic reversion Fin(-)-Fin+.

It has been shown that the rad1-5 mutation which alters excision repair in Saccharomyces cerevisiae yeast increased reversion frequency of the ochre mutation his7-1 and the frequency of intragenic mitotic recombination in the LYS2 gene induced by 2-aminofluorene and 2-acetylaminofluorene, as compared with the wild type strains activated in vitro by 39 mix from chicken liver.

The effect of zixoryn, a hepatic inductor of cytochrome P-450, on the pharmacokinetics of antipyrine in intact and sensibilized guinea-pigs was studied. It was found that sensibilization of albumin increased the half-time (T1/2), AUC and decreased the total body clearance (Clt) of antipyrine and the renal clearance (Clr) of metabolites in urine. The administration of zixoryn in sensibilized animals decreased T1/2 and AUC and increased the clearance of antipyrine and its metabolites.

The effect of adamanthylamides of 1,3-diphenylptrazol-4-carbonic acids on the system of the liver microsomal monoxygenases was studied. A potent induction of the liver cytochrome P-450 by 1,3-diphenylpyrazol-5-methyl-4-carbonic acid, N-methyl-N-(adamant-1-il)amide was found. As a consequence of the induction of the liver cytochrome P-450, the compound reduced by 40% the degree of the delayed type hypersensitivity in mice.

On the 3rd day after the last administration of phenobarbital (50 mg/kg orally, 4 days), benzonal (35 mg/kg orally, 4 days), zixorine (200 mg/kg orally, 4 days) and 3-methylcholanthrene (20 mg/kg subcutaneously, 2 days) the rats exhibited a decrease of iodamide secretion in the kidneys. The administration of zixorine to the dog (200 mg orally, 6 days) led to a significant decrease of iodamide transport in the first two weeks after discontinuation of the drug administration.

Paraquat action on glutathione reductase activity and intratissue distribution in the liver of intact rats and also in the animals antenatally treated with the given herbicide was studied by some biochemical and histochemical methods. It has been ascertained that paraquat injection into intact animals promotes the increase in the intracellular enzyme level, development of glutathione reductase staining of hepatocyte nuclei, diffuse distribution of the staining along the lobe. In rats antenatally treated with paraquat acute priming does not induce glutathione reductase. In these conditions a mosaic distribution of this enzyme is observed in the hepatic tissue.

The effect of diet on induction of monooxygenases and distribution of label from 2-14C-lysine in fractions of liver homogenate, muscle homogenate and blood of male rats treated with phenobarbital (80 mg/kg, three days) was studied. 2-14C-lysine was injected intraperitoneally 24 h before the first injection of phenobarbital. It was demonstrated that monoxygenase induction, increase of relative liver weight and incorporation of label from 2-14C-lysine into fractions of liver homogenate in phenobarbital-treated rats were more pronounced as compared with the similarly treated rats that were fed a balanced diet. The possibility of mobilization of deficient essential components to liver from other organs and tissues for maintenance of monoxygenase induction is discussed.

In experiments on rats and dogs it was shown that administration of phenobarbital (20 and 50 mg/kg orally, 4 days), benzonal (35 mg/kg, orally, 4 days), zixorine (200 mg/kg orally, 4 days) and 3-methylcholanthrene (20 mg/kg subcutaneously, 2 days) caused on the 3rd day following the last administration of the drug a reduction of verografine secretion in the kidneys. After administration of phenobarbital to dogs (20 mg/kg orally, 4 days) a decrease of renal transport of verografine within 4-5 weeks was observed.

The effect of single and chronic administration of hydrocortisone on the thymus proteinase activity in the alkaline pH range was studied on rats. The presence in the thymus of the glucocorticoid-sensitive alkaline proteinase system induced by hydrocortisone was shown. A decrease of the activity of the system in the adrenalectomized animals was found. The possible relationship between the thymolytic effects of hydrocortisone and the increased activity of the alkaline proteinase systems of the thymus is concluded.

It has been found that the Soviet anticonvulsant drug Benzonal is an inducer of the liver cytochrome P-450 of the phenobarbital type. The drug causes formation of the cytochrome P-450 form which is immunologically identical to the phenobarbital inducible form of the hemoprotein with identical molecular mass determined with the SDS-gel electrophoresis method in PAAG. The microsomes, obtained from the rats treated with Benzonal display increased rates of metabolism of 7-pentoxiresorufin and 16 beta-hydroxylation of androstenedione which are specific substrates for the cytochrome P-450b.

A study of tumors induced in mice by transplacental exposure to 7,12-dimethylbenz(a)anthracene (DMBA) alone or in combination with postnatal tissue-specific promotion showed skin and liver tumor development to be associated with cellular Ha-ras oncogene activation in a large percentage of cases. As shown by Xba I RFLP, oncogene activation was caused by T for A substitution at the second position of codon 61. The said mutation was traced in DMBA-induced tumors of the liver alone but not in spontaneous hepatomas. The results of the study showed the role of oncogene activation in cancer development to be tissue-specific.

A study was made of effects of aldosterone, aldosterone+dexamethasone, and aldosterone+spironolactone on Na,K-ATPase mRNA expression in renal cortex of adult and 10 day old rats, when kidney is not sensitive to the hormone injection. It is shown that hormonal induction of synthesis of Na,K-pump mRNA occurs in the early postnatal period apart from mineral corticoid receptors. It seems probable that aldosterone exerts its action in 10 day old rats by interaction with glucocorticoid receptors inducing synthesis of different amounts of alpha- and beta-subunits of Na,K-ATPase.

The effect of cyclic 3',5'-adenosine monophosphate (cAMP) on the rate of beta-galactosidase biosynthesis was studied in the cells of Escherichia coli M-17 growing in MPB and mineral media with glucose and maltose, i.e. under the conditions of various catabolite repression, as well as upon lac-operon induction by isopropyl-beta-D-galactopyranoside (IPGP). The stimulating action of exogenous cAMP was found only in a medium with salts and glucose. The induction by IPGP was highest during the growth in a medium with glucose and maltose. When the medium contained IPGP, cAMP accelerated the enzyme synthesis in all media, but only at the early growth phases, while cAMP eliminated the effect of IPGP at the stationary phase of growth. The regulation of beta-galactosidase biosynthesis by cAMP demonstrated for the first time that this effect depended on the physiological state of E. coli: the expression of catabolite-sensitive E. coli genes was subject to both positive and negative regulation in one and the same inducible system. The effect exerted by cAMP depended on the nature of a carbon source in the growth medium.