[Toxicity of ethyl-3-(8-fluoro-2-methyl-2,3,4,5-tetrahydropyrido[4,3-b]indol-5-yl)-propionate dihydrochloride possessing antiallergic properties].

The toxicity of new gamma-carboline derivative [ethyl 3-(8-fluoro-2-methyl-2,3,4,5-tetrahydro-1H-gamma-carbolin-5-yl)-propionate dihydrochloride, CD-008-040] has been studied.

[Anti-allergic properties of a novel ethyl 3-(8-fluoro-2-methyl-2,3,4,5-tetrahydropyrido[4,3-b]indol-5-yl)propionate dihydrochloride].

The influence of ethyl-3-(8-fluoro-2-methyl-2,3,4,5-tetrahydro-1H-gamma-carboline-5-yl)propionate dihydrochloride belonging to the class of gamma-carbolines on the allergic reactions (inflammation and systemic anaphylaxis) has been studied on laboratory animals. It was established that the given substance administered in a dose of 5 - 20 mg/kg exhibits a pronounced antiallergic action. Unlike many other antihistamine drugs, this gamma-carboline derivative probably does not produce sedative effect.

[Binding of nuclear proteins with segments of the c-fos gene promotor, localized in position (-465)-(-435) correlates with cell proliferation]. / Sviazyvanie iadernykh belkov s uchastkom promotora gena c-fos, lokalizovannym v pozitsii (-464)-(-435), korreliruet s kletochnoi proliferatsiei.

Using gel-retardation assay we have investigated binding of nuclear proteins to the mouse c-fos promoter region 30 b.p. long (nucleotides (-464) - (-435) from TATA-box), localized upstream of PDGF-dependent induction element. It was found that some factors from nuclear extracts of various human and murine cells bind to this promoter region. After gel-retardation of DNA- protein complexes from nuclear extracts of quiescent and stimulated with 20% fetal calf serum cells we observed only one retarded band, while after gel-retardation of DNA-protein complexes from proliferating pseudonormal and tumorigenic cells we observed the appearance of additional retarded band with higher mobility in PAAG. We also have determined the molecular weights of factors interacting with investigated c-fos promoter region by affinity modification method. The molecular weights of both factors are 59 kDa. The equality of molecular weights of investigated factors suggests that these factors might be different forms of one nuclear protein.

[Nuclear peptides, specifically binding oligonucleotides]. / Iadernye peptidy, spetsifichno sviazyvaiushchie oligonukleotidy.

Interaction of alkylating derivatives of oligonucleotides with nuclear extracts from mammalian cells has been investigated. Three modified 1.5-, 3.0-, and 6.0-kDa proteins were detected in nuclear extracts from human and murine cells. The 1.5-kDa and 3.0-kDa proteins were also detected in insect, plant, yeast, and bacterial cells. The ubiquity of the proteins suggests their important role in cellular metabolism.

[Regulation of the expression of the c-fos gene in cells, reverting from being transformed to the pseudonormal phenotype]. / Reguliatsiia ékspressii gena c-fos v kletkakh, revertiruiushchikh ot transformirovannogo k psevdonormal'nomu fenotipu.

Regulation of c-fos expression in mice sarcoma cell lines CBA and C3H was investigated. Each of the cell lines was represented by a pair of clones: the tumorigenic and the one, which was produced from it by cloning. It was found, that c-fos expression in cells of the pseudonormal phenotype was similar to that in the normal fibroblasts. Experiments with cells reverted to pseudonormal phenotype transfected transiently or permanently with an indicator plasmid fos-cat have shown, that a 600 bp sequence of the c-fos promotor including the TATA site, provides the expression level of the chloramphenicol acetyltransferase, correlating with the level of the c-fos mRNA expression. In the tumorigenic cells, permanent high activity of the cat gene expression was observed which was comparable to that in the normal fibroblasts stimulated by the embrionic serum or TPA. Activity of the transcription factors interacting with regulatory elements SRE, DSE, TRE did not correlate with the c-fos expression level in all the cells.