DNA Methylation, Deamination, and Translesion Synthesis Combine to Generate Footprint Mutations in Cancer Driver Genes in B-Cell Derived Lymphomas and Other Cancers.

Cancer genomes harbor numerous genomic alterations and many cancers accumulate thousands of nucleotide sequence variations. A prominent fraction of these mutations arises as a consequence of the off-target activity of DNA/RNA editing cytosine deaminases followed by the replication/repair of edited sites by DNA polymerases (pol), as deduced from the analysis of the DNA sequence context of mutations in different tumor tissues. We have used the weight matrix (sequence profile) approach to analyze mutagenesis due to Activation Induced Deaminase (AID) and two error-prone DNA polymerases.

[Influence of isoniazid complex with A-I apolipoprotein on activity of lysosomal enzymes in mice with tuberculous inflammation model].

It is established that isoniazid (isonicotinic acid hydrazide) can interact with A-I apolipoprotein to form a complex, which can be considered as the transport form of the preparation. The use of this complex for the treatment of mice with BCG-induced tuberculous inflammation led to an increase in the free activities of acid phosphatase and cathepsin D in the liver, which was decreased under the action of mycobacteria and the free form of isoniazid. The isoniazid complex with A-I apolipoprotein exhibited more expressed anti-inflammatory effect (estimated by the activity of chitotriosidase in blood serum) as compared to the free drug.

[High-density lipoproteins as a form of daunorubicin transport in hepatoma cells of mice].

The efficiency of using high-density lipoproteins (HDLPs) as the transport form of an antineoplastic drug daunorubicin (rubomycin hydrochloride, daunoxome) has been shown on the culture of HA-1 hepatoma cells of mice. The use of HDLPs in a complex with daunorubicin led to an increase in the efficiency of drug transport and cytotoxic action with respect to tumor cells in comparison with hepatocytes of healthy animals.

[The analysis of interaction between lipoproteins and steroid hormones].

Using the methods of ultracentrifugation, gel-filtration and fluorescence quenching, we demonstrated, that plasma lipoproteins bind steroid hormones and can therefore play a role of their active transport form in an organism. High density lipoproteins have revealed the highest affinity to steroids for. It has been found, that protein component of lipoproteins takes part in the formation of lipoprotein-steroid complex.

[Role of tumor-associated macrophages in the regulation of protein biosynthesis in Ehrlich carcinoma cells].

The paper discusses the role of peritoneal macrophages in uptake and metabolic degradation of high-density proteins of lipoproteins in mice with Ehrlich ascites carcinoma. These processes were found to be influenced by cortisol. Distinctions in spectra of endocellular proteins in tumor-associated macrophages and peritoneal ones in intact mice were identified and, in particular, relative to apolipoprotein E level.

[Mechanisms of interaction of tetrahydrocortisol and its complex with apolipoprotein A-I and DNA regulatory cis-elements of CC(GCC)5/GG(CGG)5 type].

An IR-spectroscopy study of the mechanism of interaction between duplex CC(GCC)5/GG (CGG)5Li2 and tetrahydrocortisol or tetrahydrocortisol-apolipoprotein A-I complex revealed the formation of hydrogen bonds between the OH group of the tetrahydrocortisol A-ring and the C=0 group of cytosine or guanine. Tetrahydrocortisol forms hydrogen bonds with the PO2-group of the duplex and with the OH-group of monosaccharide. The interaction of tetrahydrocortisol and apolipoprotein A-I with the duplex occurs at the same active site, namely, with the C=O-group of bases.

[Effect of apolipoprotein A-1 containing steroid hormones on DNA and protein biosynthesis in cells of ascitic hepatoma HA-1].

The rate of DNA and protein biosynthesis in murine hepatoma HA-1 was accelerated when steroid hormones, containing a reduced delta4,3-keto group in the A-ring, were used in combination with apolipoprotein A-1. That was demonstrated for apolipoprotein A-1 complexes with dehydroepiandrosterone, dehydroepiandrosterone sulfate and tetrahydrocortisol. Apolipoprotein A-1 complexes serve as a vehicle for steroids penetration into cells to influence protein biosynthesis.

[Interaction of tetrahydrocortisol-apolipoprotein A-I complex with eukaryotic DNA and with single-stranded oligonucleotides].

The complex formed by tetrahydrocortisol (THC) and apolipoprotein A-I (ApoAI) specifically interacts with eukaryotic DNA from rat liver. Taken together, physical and chemical data and the results of small-angle X-ray scattering analysis show that interaction of the THC-ApoAI complex with eukaryotic DNA results in deformation of the DNA double helix. Single-stranded fragments were demonstrated to cause deformation of the double helix.

[Interaction of eukaryotic DNA with apolipoprotein A-I and its complexes with glucocorticoids].

A biochemically active complex of apolipoprotein A-I with tetrahydrocortisol was revealed, which increases gene expression in hepatocytes. It was shown by the method of fluorescent probe that titration of rat liver DNA by the apolipoprotein A-I-tetrahydrocortisol complex leads to the appearance of single-stranded fragments. The effect of the complex on the secondary structure of native DNA was confirmed by the method of small-angle X-ray scattering.

[Anomalous change in the specific conductivity in lipoproteins at around physiologic temperatures].

Studying the temperature dependence of conductivity sigma of rat and human lipoproteins and apoprotein A-I fractions revealed an anomalous region in the range of temperatures (35-38) +/- 0.5 degree C. The activation energy delta H and temperature coefficient sigma (delta sigma/delta T) on both sides of Tc and the heat of transition (delta H of transition) were calculated.

[Enzyme-linked immunosorbent assay for apolipoproteins A-I and B in the urine of patients with nephrotic syndrome].

Enzyme-linked immunosorbent assay (ELISA) has been used for measuring apolipoproteins A-I and B in the urine. ApoB is absent in urine of healthy subjects, and apoA-I is determined in trace quantity. In patients with chronic glomerulonephritis quantity of apoA-I in urine was 117 times as much as in control group.

[Effect of plasma lipoproteins and apolipoprotein A-I on lipopolysaccharide-induced production of reactive oxygen metabolites by Kupffer cells of the rat].

The effects of plasma lipoproteins on LPS-induced production of reactive oxygen intermediates (ROI) in Kupffer cells isolated from livers of zymosan-treated rats, have been studied. ROI production was low in normal Kupffer cells but increased 18-fold by LPS in Kupffer cells from zymosan-treated rats. However, preincubation of LPS with rat serum, low density lipoproteins, high density lipoproteins (HDL3) and apolipoprotein A-I (apoA-I) decreased the LPS-induced production of ROI by 1.

[The neuroendocrine mechanisms of the development of the anovulatory hyperandrogenic syndrome in rats].

The anovulatory syndrome in adult female rats occurred after subcutaneous implantation of silastic capsules with testosterone. Acceleration of testosterone conversion into estradiol in the hypothalamus, suppression of pituitary LH responsiveness to LHRH, increase of blood plasma bioactive LH, estrous cycle disorder as well as morphological changes in ovaries demonstrate the alterations in neuroendocrine control of ovulation.

[Social aspects of pathology].

Pathology is a basis science not only for theoretical and practical medicine but also for health service. Autopsies of the persons dying in the hospitals and outpatient departments would be the most valuable and objective indices of treatment quality during the period of transition to insurance medicine. The most efficient social functioning of pathology will be possible only if the pathology service is centralized.

[The receptor-mediated endocytosis of complexes of colloidal gold with high-density lipoproteins by the sinusoidal cells of the isolated rat liver].

Rat hepatic sinusoidal cells absorption of native high-density lipoproteins was studied by electron microscope. Visualization of the endocytosis process was achieved by binding of lipoprotein particles and colloidal gold. The study was carried out on isolated liver perfusing by oxygenated nutritional media which consist of colloidal gold-lipoproteins conjugates.

[Lipid biosynthesis and metabolism of native and acetylated low density lipoproteins in macrophages stimulated by zymosan in vivo and in vitro].

The effects of zymosan on lipid metabolism in mouse peritoneal macrophages (MPM) in vitro and in vivo were studied with special reference to the following parameters: i) 14C-oleate incorporation into cholesteryl esters (CE), triglycerides (TG), and phospholipids (PL) in MPM incubated with low density lipoproteins (LDL) and acetylated LDL; ii) cholesteryl-14C-oleate-acetyl LDL uptake and 125I-acetyl LDL degradation; iii) oxidative modification of LDL. Zymosan administered to mice caused significant stimulation of 14C-oleate incorporation into CE, TG, and PL with no effect on 3H-cholesterol (Ch) incorporation into CE or 3H-glycerol incorporation into TG and PL in MPM. The 14C-oleate incorporation into cellular lipids was unaffected by 18-hour incubation of MPM with zymosan (100-500 micrograms/ml) but increased after incubation of unstimulated MPM with blood serum and peritoneal fluid harvested harvested from zymosan-treated mice.

[Quantitative characteristics of interactions of blood lipoproteins and steroid hormones].

Human and serum lipoproteins interaction with steroid hormones (corticosterone and hydrocortisone) were studied. Methods of fluorescence quenching titration and equilibrium dialysis were used for quantitative evaluation of VLDL, LDL and HDL glucocorticoids binding ability. Association constants were found to be 0.

[Detection of apoprotein A-1 immunoreactivity in chromatin of rat hepatocytes].

The binding of 125I-labeled lipoproteins to subcellular structures of rat hepatocytes was studied. The protein component of HDL, LDL, and VLDL was found in large and small membranes, nuclei, mitochondria, lysosomes, microsomes, and cell cytosol. The presence in liver nuclear chromatin of proteins immunochemically related to apoA-1 was demonstrated by solid phase immunoenzymatic analysis, dot immunoanalysis, and immunoelectroblotting.

[Cholesterol esterification in tissues and change in the apoprotein spectrum in rat blood under the effect of auto-oxidized cholesterol].

Influence of autooxidized cholesterol (Ch) products on accumulation of cholesterol esters (ChE) in liver and aorta tissues as well as alteration of the apolipoprotein spectrum in low density and very low density (LDL and VLDL) lipoproteins in blood plasma was studied in rats treated with purified Ch (ChP-rats) and with oxidized Ch containing 5% 25-hydroxyCh and 3% 7-ketoCh (ChO-rats). Increase of ChE content in liver tissue of ChO-rats resulted in two-fold activation of acyl-CoA-cholesterol-O-acyltransferase (ACAT) in liver microsomes as compared with the enzymatic activity rate in ChP-rats. As shown by polyacrylamide gel electrophoresis content of apoE in VLDL and LDL of ChO-rats was 1,5-fold higher as compared with that of ChP-rats.

[Interaction of lipoproteins in blood serum with steroid hormones].

Interaction of human and serum lipoproteins with steroid hormones (corticosterone and cortisol) was studied. Methods of fluorescence quenching titration and equilibrium dialysis were used for quantitative evaluation of VLDL, LDL and HDL glucocorticoid-binding ability. Association constants were found to be 0.