[Clinical and anamnestic analysis of multiple primary neoplasms with lesions of the endometrium in women of the Novosibirsk region].

Based on the study of 60 women who were treated at the gynecology department of the Novosibirsk Regional Oncology Dispensary from 2003 to 2013 with a diagnosis of primary multiple synchronous and metachronous neoplasia with endometrial lesion it was found that the most common risk factors for this disease could be considered: overweight and obesity; late age at onset of menarche; late age of menopause; concomitant cardiovascular diseases and disorders of the endocrine metabolism.

[Microrna, evolution and cancer].

MicroRNAs are known as a posttranscriptional negative regulators of gene expression by binding to the 3'UTP of target mRNAs in cytoplasm. More than 1600 microRNAs expressed in human cells, are involved in the regulation of embryogenesis, differentiation, cell cycle, apoptosis, senescence, thus determining cell fate. Up to 60 % of protein coding genes are under their control. Various sets of microRNAs found in different human tissues under normal and pathological conditions, including cancer, suggest that miRNAs are involved in most cellular pathways. To date, there is no doubt that regulatory potential of the genome is largely determined by miRNAs. In our study, we performed a comparative phylogenetic analysis of the origin and evolution of the total set of 1048 miRNAs in the human genome and investigated the role of certain miRNAs in carcinogenesis of thyroid and mammary glands, as potential diagnostic and prognostic biomarkers of malignancy. Analysis of phylogenetic distribution of miRNAs in the human genome has shown four peaks of appearance of new miRNA genes in the evolution from Methazoa to H. sapiens. The highest amount of new miRNA genes appeared after divergence of H. s. from common ancestor with P. t. Expansion of transposable elements in genome was accompanied by the origin of new miRNA genes on the basis of their sequences. More than 14 % from 1600 miRNAs of human genome originated from mobile elements and still remain. Profiles of expression of 5 miRNAs, pertaining to oncomicroRNAs - miR-21, -221, -222, -155 and -205 - allow distinguishing ductal invasive carcinoma of mammary gland and thyroid papillary carcinoma. The data obtained suggest different ways and roles of participation of the same miRNAs in carcinogenesis of thyroid and mammary glands. So, these miRNAs and profiles of their expression might be used in the diagnosis and prognosis of cancer.

[Tissue-specific expression of hormonal carcinogenesis target genes in rats treated with polycyclic aromatic hydrocarbons].

We have investigated the effect of polycyclic aromatic hydrocarbons (PAHs) on estrogen-metabolizing genes CYP1A1, CYP1B1, CYP19 and ERalpha and cyclin D1 genes, which control of cell division in estrogen-depended tissues. Treatment of rats with benzo(a)pyren (BP) or 3-methylcholantrene (MC) significantly up-regulated CYP1A1, CYP1B1 gene expression in liver, uterus and ovary, whereas alfa-naphthoflavone (alpha-NF) did not have any effect. The high level of aromatase gene (CYP19) expression was detected in ovary only. Treatment of rats with BP or MC significantly down-regulated expression of this gene (15- and 5,5-fold, respectively), whereas alpha-NF did not have any effect. BP produced an increase in ERalpha and cyclin D1 gene expression in rat liver. This effect was not seen with MC and alpha-NF. ERalpha and cyclin D1 mRNA levels were unchanged in uterus of rats after PAHs treatment. On the other hand, BP treatment caused an increase of the ERalpha and cyclin D1 mRNA levels (3,5- and 2,5-fold, respectively) in ovary, whereas MC and alpha-NF did not have any effects. Thus, our results give evidence for tissue-specific effects of PAHs on expression of genes, which participate in hormonal carcinogenesis. Moreover, the fact that BP and MC treatment affects the expression of estrogen-metabolizing genes and genes, which control of cell division, supports the view that PAHs may be one of the causes of endocrine disorder and consequent hormonal carcinogenesis.

[Remote effects of Aroclor 1254 on the rat liver microsomal monooxygenase activity in acute pancreatitis]. / Vliianie Arokhlora 1254 na mikrosomal'nuiu monooksigenaznuiu sistemu pecheni krys pri ostrom pankreatite v otdalennye sroki.

Constitutive activities of the liver cytochromes P450 1A1, 1A2, 2C6 and 2B1 were lower in rats with the acute experimental pancreatitis during ten days of this disease. In rats pretreated with a single dose of Arochlor 1254 on the second day of pancreatitis activities of these enzymes remained elevated to the tenth day. Thus, acute pancreatitis caused long-term suppression of microsomal monooxygenase system, whereas induction by Arochlor 1254 increased cytochromes P450 activity in both control animals and in rats with pancreatitis.

[Changes in the microsomal monooxygenase system of the rat liver in acute pancreatitis and during induction by Aroclor 1254]. / Izmenenie mikrosomal'noi monooksigenaznoi sistemy pecheni krys pri ostrom pankreatite i induktsii Arokhlorom 1254.

The effect of Arochlor 1254 treatment of rats on activities of cytochrome P450 isoforms 1A1, 1A2, 2C6 was investigated under conditions of acute pancreatitis. Irrespectively to the scheme of Arochlor 1254 administration (before the development of pancreatitis, and at various periods after its provocation) cytochrome P450 activities were higher than in corresponding controls.

[mRNA level and cytochrome P450 1A activity in the liver of C57BL mice induced by various xenobiotics]. / Uroven' mRNK i aktivnost' tsitokhromov P450 1A v pecheni myshei linii C57BL pri induktsii razlichnymi ksenobiotikami.

The rate of hepatic cytochrome P450 Cypla1 and Cyp1a2 induction was investigated in C57BL male mice during induction with o-aminoazotoluene (OAT), benzo[a]pyrene (BP) and 1,4-dihydroxyanthraquinone (AQ). The Cypla1 mPNA level determined by quantitative RT-competitive PCR increased more than three orders of magnitude during induction with OAT and BP compared with untreated animals and remained unchanged during induction with AQ. The Cypla2 mRNA level was only 8.5, 18.7 and 1.9 times higher during induction with OAT, BP and AQ respectively than in untreated mice. At the same time 7-Ethoxyresorufin-O-deethylase (EROD) and 7-Methoxyresorufin-O-demethylase (MROD) activities of Cypla were also investigated in liver. The increase of Cypla1 mRNA level correlated with the increase of EROD activity. This suggests involvement of the transcriptional mechanism of the inducibility of this enzyme. In the case of Cypla2 there was insignificant increase of its mRNA level but high catalytic activity registered in liver in response to injection of the inductor of MR metabolism. This can imply the posttranscriptional mechanism of Cypla2 regulation. During induction with AQ the Cypla1 mRNA level remained unchanged, but the EROD activity increased almost 20-fold. The latter suggests insufficient specificity of this substrate for Cypla1. Thus, on the basis of the data obtained, the mRNA level can be considered as more accurate estimation of Cypla1 and Cypla2 inducibility, than the determination of the enzyme activity.

[Change in the rat liver microsomal monooxygenase system upon induction with phenobarbital in acute pancreatitis]. / Izmenenie mikrosomal'noi monooksigenaznoi sistemy pecheni krys pri induktsii fenobarbitalom na fone ostrogo pankreatita.

While injecting phenobarbital (PB) into the rats, on the second day of an experimental pancreatitis, cytochrome P450 2B1 and 2C6 activities were found, on the forth day of disease, as being considerably higher in comparison with data obtained in sham-operated control animals. On the tenth day of the acute pancreatitis (in three days upon having the induction canceled), activity of the cytochrome P450 isozymes was lower than that of control animals. Thus, the rats with acute pancreatitis, are characterized by an increased indycibility of liver monooxygenases. In addition, a release from induction (decrease of these activities upon having the induction canceled) proceeds faster than that in control animals.

[Interstrain differences in enzymatic activity of CYP2B1 and expression of its gene in the rat liver during induction with phenobarbital and triphenyldioxane]. / Mezhlineinye razlichiia v fermentativnoi aktivnosti CYP2B1 i ékspressii ego gena v pecheni krys pri induktsii fenobarbitalom i trifenildioksanom.

The interstrain differences in hepatic 7-pentoxyresorufin-O-dealkylase and 16 beta-androstendione hydroxylase activities specific for cytochrome P450 2B1 have been found in Sprague-Dawley, Brattleboro and Wistar rats treated with with phenobarbital, triphenyldioxane. Similar differences were found in the accumulation of corresponding mRNAs suggesting differences in expression of cytochrome P450 gene. Analysis of the enzymatic activity and mRNA level revealed positive correlation between these parameters. Thus, differences in transcriptional activity of CYP2B1 gene during induction by phenobarbital and triphenyldioxane may be one of reasons for interstrain differences between enzymatic activities of rat liver cytochrome P4502B1.

[The effect of low-intensity physical therapeutic factors on the microsomal oxidative systems of the liver in an experiment]. / Vliianie nizkointensivnykh fizicheskikh lechebnykh faktorov na mikrosomal'nye okislitel'nye sistemy pecheni v éksperimente.

The authors' rat experiments have shown that inhibition of pro-oxidant reactions in hepatocyte microsomal fraction in response to hepatic exposure to low-intensive IR-laser radiation and low-intensity ultrasound combines with multidirectional action of these factors on the basic enzymes of the other oxidant system of hepatocyte microsomes--cytochrome P-450-dependent monooxigenase system.

[Dynamics of accumulation of CYP2B mRNA in the liver of rats from various strains during induction with xenobiotics]. / Dinamika nakopleniia mRNK dlia CYP2B v pecheni krys razlichnykh linii vo vremia induktsii ksenobiotikami.

The transcription level of CYP2B1/2 gene in the liver of Sprague-Dawley (SD), Brattleboro (BL) and Wistar (W) rats treated with isosafrol (IS), Arochlor 1254 (AC), phenobarbital (PB) and triphenildioxane (TPD) was studied. The quantity of CYP2B1/2 mRNA was assessed by dot-blot analysis at 18, 48 and 72 hours after inducers administration. The mRNA level in SD and BL rats treated with PB reached its maximum by 18 hours followed by fast decline. For W strain the amount of mRNA reached maximum by 48 hours after treatment. After TPD treatment this parameter for SD, W rats reached maximum by 18 hours, while for BL-72 hours. No differences in the mRNA amount in rats treated with IS and AC were detected. We are not aware of any other data concerning the dynamics of CYP2B1/2 mRNA accumulation during IS-induction. We showed that in this case a maximum of mRNA was reached by 18 hours. Thus, we revealed inducer- and strain-dependent of differences in mRNA accumulation dynamics.

[Change in activity of microsomal cytochrome P-450-dependent monooxygenases from rat liver exposed to chronic low doses of radiation]. / Izmenenie aktivnosti mikrosomal'nykh tsitokhrom-P-450-zavisimykh monoksigenaz pecheni krys pod vliianiem khonicheskogo vozdeistviia malykh doz radiatsii.

The activity changes of cytochrome P-450-dependent monooxygenases of hepatic microsomal fraction were studied in, experimental animals after prolonged application (1 month) of low radiation doses (0.258 mkl/kg). The obtained results show the increase in catalytic activities of main forms of cytochrome P-450, participating in steroid hydroxylation, as well as the decrease in total content of cytochrome P-450 in hepatic microsomal fraction and the lowering of its demethylase activity.

[Induction of cytochrome P-450 1A1 in rat liver by ultrasound]. / Induktsiia tsitokhorma P-450 1A1 v pecheni krys ultrazvukom.

Rat liver monooxygenase activities, such as androstenedione (AD)-hydroxylase, pentoxyresorufin (PR)- and ethoxyresorufin (ER)-O-deethylases have been studied under contact application of ultrasound (US). In the livers of US-treated rats the AD-hydroxylase activity did not differ from the control, thus suggesting that CYP2A1, CYP2B1, CYP2C11, CYP3A1 were not induced. The rate of ER-deethylation increased from 100 in control up to 300 pmol/min/mg in US-treated rats. Western blot analysis revealed also the CYP1A1 induction in US-treated rats which was absent in untreated animals. The mRNA level for CYP1A1 in the livers of US-treated rats increased from 0.5 up to 6.0 fmol mRNA/total RNA but did not change for CYP1A2. The results obtained provide evidence for the nonchemical induction of CYP4501A1 which is known to be induced by polycyclic aromatic compounds as well as by some other compounds.