[Dispermic androgenesis in sturgeons with the help of cryopreserved sperm: production of androgenetic hybrids between Siberian and Russian sturgeons].

Dispermic androgenesis was used to produce, for the first time, an androgenetic progeny of the Siberian sturgeon (Acipenser baerii) and the androgenetic nuclear cytoplasmic hybrids (Siberian sturgeon, A. baerii x Russian sturgeon, A. gueldenstaedtii) using cryopreserved sperm. Microsatellite DNA analysis confirmed exclusively paternal inheritance in the androgenetic progeny of Siberian sturgeon. Heterozygotes for certain microsatellite loci were detected among the androgenetic hybrids, thereby confirming a dispermic nature of androgenesis. According to the data of comparative morphological analysis, the obtained androgenetic hybrid, by the age of 15 months old, was completely identical to the paternal species. Both a female and a male were detected in the androgenetic sturgeon progenies, which is of interest for producing bisexual progenies via androgenesis. The data of this study confirm the feasibility of dispermic androgenesis using cryopreserved sperm to preserve and recover the gene pools of endangered sturgeon species.

Nitroxyl antioxidant TPPA-TEMPO increases the efficacy of antitumor therapy on the model of transplantable mouse tumor.

Nitroxyl antioxidant 4-triphenylphosphonioacetamido-2,2,6,6-tetramethylpiperidine-1-oxyl (TPPA-TEMPO) was synthesized from 4-chloroacetamido-2,2,6,6-tetramethylpiperidine-1-oxyl chloride and triphenylphosphine. Systemic administration of TPPA-TEMPO in the subtoxic dose to mice with lymphosarcoma inhibited tumor growth, but did not prolong animal lifespan. Combined treatment with TPPA-TEMPO and cyclophosphamide increased the efficacy of antitumor therapy: it prolonged animal lifespan and increased the number of recovered mice.

Fractional composition of blood serum lipoproteins in mice and rats with Triton WR 1339-induced lipemia.

We compared fractional composition of blood serum lipoproteins (LP) in female ICR mice and Wistar rats induced by single administration of a nonionic detergent Triton WR 1339 in doses of 300 and 500 mg/kg. Lipemia in animals of both species was characterized by a sharp increase in the concentration of cholesterol and, particularly, of triglycerides in blood serum lipoproteins by the 24th hour after administration of the detergent. We revealed a significant increase in the concentrations of atherogenic VLDL cholesterol (due to VLDL2), intermediate density lipoproteins, and LDL. These changes were more pronounced in rats. The model of lipemia can be used to study the role of fractional composition of lipoproteins and, particularly, of triglycerides in the pathogenesis of atherosclerosis. Moreover, this model holds much promise for evaluation of the efficiency of hypolipidemic drugs (statins and fibrates) in normalizing the increased level of atherogenic cholesterol of VLDL and LDL.

Inhibitor of indoleamine-2,3-dioxygenase 1-methyl-D-tryptophan can stimulate the growth of immunogenic tumors.

We studied the effect of 1-methyl-D-tryptophan, an inhibitor of indoleamine-2,3-dioxygenase, on the growth of transplanted hepatocarcinoma-29 in C3HA mice. Hepatocarcinoma-29 transplanted into the thigh muscles undergoes immunological rejection in more than 50% non-syngeneic recipients. Chronic local administration of 1-methyl-D-tryptophan promotes progressive growth of the tumor in recipient mice leading to 100% animal death. The stimulating effect of 1-methyl-D-tryptophan on tumor growth is discussed.

[Effect of hepatocarcinogenicity of estragole on the glucocorticoid-mediated induction of liver-specific enzymes and the activity of the transcription factors FOXA and HNF4 in the liver of mouse and rat].

The carcinogenic effects of estragole in mice of the earlier unexplored strain ICR has been studied. It has been shown that there is a distinct correlation between the extent of inhibition of glucocorticoid-mediated induction of tyrosine aminotransferase and trypthophan oxygenase after acute administration of estragole and the frequency of liver tumors after estragole exposure. Estragole inhibits the induction of these enzymes only in female mice, but not in male mice and rats. DNA-binding activities of liver-enriched transcription factors were investigated on carcinogen-susceptible and -resistant animals. Estragole decreases the HNF4 (hepatic nuclear factor 4) and FOXA DNA-binding activities only in susceptible female mice, but not in nonsusceptible male mice and rats and does not influence the C/EBP and HNF1 activities. Pentachlorophenol, which prevents the hepatocarcinogenic effect of estragole, abolishes its inhibitory effect on tyrosine aminotransferase and trypthophan oxygenase glucocorticoid induction and restores the FOXA and HNF4 DNA-binding activities. The parallelism between the hepatocarcinogenic effects of estragole and the inhibition of FOXA and HNF4 DNA-binding activities serves as an additional argument for the involvement of these factors in the mechanisms of tumor suppression in the liver.

[Influence of age and sex on hepatotoxic and hypothermic effects of estrogole in mice].

Some physiological effects of estragole under a single intraperitoneal injection in oil solution were studied in GR mice; elevation of blood aminotransferases activity, body temperature and animals lethality were registered. At a dose of 600 mg/kg, estragole killed 100% sucklings of both sexes and 90% adult females but no any adult male. The males aquire resistance to estragole at the time of maturation. Exogenous testosterone administered at the dose of 50 mg/kg 4-2 days earlier increases the resistance of female mice to estragole up to its level in males. However, neonatally androgenized females are as sensitive to the toxic action of estragole as the males. At the dose of 900 mg/kg, estragole defeats adult males as well: significant elevation of aminotransferase activities in their blood is indicative of this. In this case, the enzyme activity reaches its peak after 2-3 days, not at the 1st day as in the case of carbon tetrachloride administration. We have discovered a strong hypothermic effect of estragole which appears to be unrelated to its hepatotoxicity and testosteron level.

[Effect of estragole on glucocorticoid induction of tyrosine aminotransferase and tryprophan oxygenase in the rat and mouse liver].

A single intraperitoneal injection of Estragole (300 mg/kg) to female ICR mice 19 hours prior to Dexamethasone induction decreased induced activities of tyrosine aminotransferase (TAT) and tryptophan oxygenase (TO) nearly to 50% of the control values. In these mice, activities of the marker enzymes of liver damage: alanine aminotransferase (ALAT) and aspartate aminotransferase (AAT) increased in the blood 1.7-2.3-fold as compared with the untreated controls. By contrast, carbon tetrachloride (100 mg/kg) increased the blood AIAT and AsAT activities 135- and 30-fold as compared with the control, but inhibited the TAT and TO induction much less than Estragole did. Estragole seems to inhibit the glucocorticoid induction of these hepatic enzymes not via the unspecific toxic damage of the liver.

Relationship between high sensitivity of suckling mice to hepatocarcinogenic and antiglucocorticoid effects of o-aminoazotoluene and diethylnitrosamine.

Suckling mice were more sensitive to the hepatocarcinogenic effect of various carcinogens compared to adult animals. After treatment with o-aminoazotoluene and diethylnitrosamine HNF3-DNA-binding capacity and glucocorticoid-induced liver tyrosine aminotransferase activity in suckling mice decreased more significantly than in adult animals.

[Different responses of DD/He and CC57BR/Mv mice to fasting]. / Neodinakovaia reaktsiia na golodanie myshei linii DD/He i CC57/BR/Mv.

Reaction to fasting of 2 mice strains differing in their sensitivity to spontaneous and induced hepatocarcinogenesis, has been investigated. It was shown that mice of both strains displayed similar stress reaction after 3-day fasting manifested in increase in blood corticosterone level; and decrease in testosterone level. At the same time, both strains demonstrated opposite changes at tissue- and enzyme levels in the liver. It was shown that DD/He mice, highly sensitive to induction of liver tumors, were characterized by significant increase in tyrosine aminotransferase (TAT) activity and reduction of lipid droplets in hepatocytes. CC57BR/Mv mice, demonstrating high frequency of spontaneous hepatomas and insensitive to induction of such tumors, were characterized by a decrease in the TAT activity and fatty infiltration of the liver.

Predisposition to alcoholism, tryptophan oxygenase activity, and structure of intron 6 in the corresponding gene of C57BL/6J, CC57BR/Mv, and BALB/cJ mice.

Crossbred CC57BR/Mv mice inherited tryptophan oxygenase gene and predisposition to alcohol consumption from parent BALB/c and C57BL mice, respectively. In CC57BR/Mv mice no relationships were found between alcohol consumption, tryptophan oxygenase activity, and single nucleotide substitutions in intron 6 of the TDO2 gene associated with predisposition to alcoholism in humans.

[Effect of the hepatocarcinogen ortho-aminoazotoluene on induction of tyrosine-aminotransferase by glucocorticoids in mouse liver]. / Vliianie gepatokantserogena orto-aminoazotoluola na induktsiiu tirozin-aminotransferazy gliukokortikoidami v pecheni myshei.

o-Aminoazotoluene (OAT) suppressed more than twofold the glucocorticoid induction of tyrosine aminotransferase (TAT) in the liver of SWR mice, which are sensitive to the hepatocarcinogenic effect of OAT, but not in resistant AKR mice. The hormone- and DNA-binding activities of the glucocorticoid receptor (GR) were not affected in either line. The OAT-dependent suppression proved to be associated with a decrease in the DNA-binding activity of HNF3 in liver cell extracts. The content of the HNF3 mRNA did not change, suggesting a posttranscriptional effect of OAT.

Elevated basal activity of tryptophan oxygenase in alcohol-preferring C57BL mice.

Tryptophan oxygenase activity in alcohol-preferring C57Bl mice and control CBA and DBA/2 mice was studied under nonstressful conditions and after glucocorticoid-induced stress. Elevated basal tryptophan oxygenase activity in C57Bl mice is probably responsible for reduced brain content of tryptophan and serotonin associated with alcohol preference.