Modified Estrogen-Progesterone Induction Method of Mammary Gland Hyperplasia in Rats.

In female Wistar rats, mammary gland hyperplasia (MGH) was modeled according to a modified protocol involving estrogen-progesterone induction and taking into account the duration of the estrous cycle of this animal species. MGH was induced over four 7-day cycles; each cycle included subcutaneous administration of 17ß-estradiol (0.5 mg/kg) for 4 days, injection of progesterone (5 mg/kg) on day 5, then 2 days without injections. In females with MGH, a significant increase in the height and diameter of the nipples of the mammary glands was recorded, two types of changes were observed in the gland tissue: tubuloalveolar and lobuloalveolar hyperplasia. The study confirmed the development of MGH in rats by a modified method.

Correction to: Evolutionarily novel genes are expressed in transgenic fish tumors and their orthologs are involved in development of progressive traits in humans.

[This corrects the article DOI: 10.1186/s13027-019-0262-5.].

Evolutionarily novel genes are expressed in transgenic fish tumors and their orthologs are involved in development of progressive traits in humans.

ABSTRACT: Earlier we suggested a new hypothesis of the possible evolutionary role of hereditary tumors (Kozlov, Evolution by tumor Neofunctionalization, 2014), and described a new class of genes - tumor specifically expressed, evolutionarily novel (TSEEN) genes - that are predicted by this hypothesis (Kozlov, Infect Agents Cancer 11:34, 2016). In this paper we studied evolutionarily novel genes expressed in fish tumors after regression, as a model of evolving organs. As evolutionarily novel genes may not yet have organismal functions, we studied the acquisition of new gene functions by comparing fish evolutionarily novel genes with their human orthologs. We found that many genes involved in development of progressive traits in humans (lung, mammary gland, placenta, ventricular septum, etc.) originated in fish and are expressed in fish tumors and tumors after regression. These findings support a possible evolutionary role of hereditary tumors, and in particular the hypothesis of evolution by tumor neofunctionalization. RESEARCH HIGHLIGHTS: Earlier we described a new class of genes that are tumor-specifically expressed and evolutionarily novel (TSEEN). As the functions of TSEEN genes are often uncertain, we decided to study TSEEN genes of fishes so that we could trace the appearance of their new functions in higher vertebrates. We found that many human genes which are involved in development of progressive traits (placenta development, mammary gland and lung development etc.,) originated in fishes and are expressed in fish tumors.

Organism-Level Tumor Models in Zebrafish Danio rerio.

Development and implementation of adequate organism-level models is one of the key elements in biomedical research that focuses on experimental oncology. Over the last decade, studies using Zebrafish (Danio rerio) have gained in popularity in this area of research. This review describes the various approaches that have been used in developing highly effective models for oncological (clinical term, better cancer or tumor) studies based on D. rerio. Priority is given to transplantation models of cancer and their application to optically transparent D. rerio lines, including clonal ones, and utilization tumors of various origins bearing fluorescent labels. The combination of tumor transplantation at organism-level models in transparent clonal D. rerio lines with fluorescent microscopy, FACS-fractionation of tumor cell subsets, and transcription analysis can result in one of the most promising research approaches in providing new information on tumor formation and growth.

[The use of the catastrophe theory method in simulating dynamics of multi-stage skin cancerogenesis]. / Ispol'zovanie metodov teorii katastrof v modelirovanii dinamiki mnogostadiinogo kantserogeneza kozhi.

A mathematical model of multistage mouse skin carcinogenesis which describes a qualitative dynamics of this phenomenon is suggested. According to this model the change in the internal state of initiated cells in promotion is determined by geometry of the Whitney catastrophe into which the surface of conditions of intact cells is transformed as a result of initiation. Molecular events underlying the convertible and unconvertible expression of a transformed phenotype by an initiated cell under the promoter action, as well as the relationship of these processes to the mechanisms of oncogene activation are discussed.

[Effects of tumor promoters and related compounds on electric relations between giant cells of the salivary glands of Chironomus tentans larvae]. / Vliianie opukholevykh promotorov i blizkikh k nim soedinenii na élektricheskuiu sviaz' mezhdu gigantskimi kletkami sliunnykh zhelez lichinok komara Chironomus tentans.

The action of 15 chemicals, being tumor-promoters and/or inhibitors of cell-to-cell communications in vitro upon electric relations between giant cells of salivary gland of the Chironomus tentans larvae are studied. It is shown that out of 11 compounds disturbing the intercellular contacts in this model, 10 chemicals are tumour-promoters (Aroclor 1254, butylated hydroxytoluene, di(ethylhexyl)phthalate, DDT, deoxycholic acid, lithocholic acid, oleic acid, anthralin, iodine-acetate, tween-80) and 1 compound (oleoyl-acetyl-glycerol) is not studied for the promoting activity. At the same time, two other tumor-promoters (phenobarbital and TPA) as well as two nontumor-promoters (phorbol and chlorpromazine) do not influence the electric relations. The possibilities of using the developed test-system for the screening of the tumour-promoters are discussed.

[Metabolic activation systems used in short-term tests for the detection of environmental carcinogens]. / Sistemy metabolicheskoi aktivatsii, primeniaemye v kratko-srochnykh testakh dlia vyiavleniia kantserogenov okruzhaiushchei sredy.

The recent data on metabolic activation of carcinogens are presented. Molecular mechanisms of activation, induction methods for systems providing biotransformation of xenobiotics as well as the comparative analysis of these systems (host, cell and cell free) are characterized from the standpoint of their use in short-term tests. The prospects of application of various metabolic activation systems are shown.

[Imprinting effect of aroclor 1254 in the metabolic activation of benz[a]pyrene by rat liver tissue]. / Imprintingovyi éffekt aroklora 1254 pri metabolicheskoi aktivatsii benz[a]pirena tkan'iu pecheni krys.

A well-known inductor of a system of multifunctional monooxygenases, the arochlor 1254, being applied to one-day rats produced an imprinting effect which was expressed in a strong and long-term increase in the metabolic activation of benzo(a)pyrene by the liver S9-fraction in the Salmonella/microsome test, as well as in the arylhydrocarbonhydroxylase activity. The imprinting was not revealed when the inductor was applied on the 9th day as well as it was not revealed for 2-acetylaminofluorene in the liver, or benzo(a)pyrene and 2-acetylaminofluorene in the kidneys, independently of the period of application.

[Trends and perspectives in environmental oncology]. / Puti razvitiia i perspektivy èkologicheskoi onkologii.

Environmental oncology is a discipline concerned with studies of multi-aspect relationships between environment and living organisms exposed to the modifying influence of carcinogenic agents. It also deals with general biological regularities involved in neoplasm development as well as their prevention in different species including man, animals and plants. Various investigations conducted at the Laboratory and supported with Russian and foreign grants (1991-1996) are briefly discussed. Among them are biotesting environmental carcinogens (aminoanthraquinons, by-products of drinking water chlorination, development of new testing systems and objects of detection involved in identification of genotoxic substances (criteria for formation of short-term test batteries and evaluation of perspectives, methods and results), investigation of xenobiotic metabolic activation (enzyme imprinting in adult animals), search for anticarcinogens (classification of carcinogenesis inhibitors, development of testing systems for modifiers selection), and establishing environment-related regularities of tumor growth. Vistas in environmental oncology development are discussed.

[Mutagenic activity of carcinogens and other chemical agents in Salmonella typhimurium tests]. / Issledovanie mutagennoi aktivnosti kantserogenov i drugikh khimicheskikh agentov v testakh na Salmonella typhimurium.

One-hundred and six chemical compounds were tested in Ames test with bacteria Salmonella typhimurium. Eight different strains (mainly, TA98 and TA100) were used. Liver S9 from Aroclor-treated rats was employed for metabolic activation. In group I comprising 51 compounds with sufficient evidence of carcinogenicity for animals, 45 were mutagenic while 6 (urethane, 1,2-dimethylhydrazine, DDT, chlorophorm, 1,4-dioxane and carbon tetrachloride) were not. In group 2 (27 noncarcinogenic compounds), 22 agents failed to exhibit mutagenicity whereas 5 (acrolein, styrene-oxide, acridine orange, I-naphthylamine and dichlormethane) revealed such activity. In groups 1 and 2, the sensitivity was 88.2, specificity--81.5 and predictive value--90%. In group 3 consisting of 28 agents used in chemical, pharmaceutical and food industries but not yet tested for mutagenicity and for the carcinogenicity of which no conclusive data are available, seven appeared to be mutagens (1-aminoanthraquinone, 2-aminoanthraquinone, 1-amino-4-chloranthraquinone, based blue, dinitrochlorbenzene, nitrosodiphenylamine and 2,3,5-trinitronaphthalene).

[Metabolic activation of chemical carcinogens by rat tissues in the perinatal period]. / Metabolicheskaia aktivatsiia khimicheskikh kantserogenov tkaniami krys v perinatal'nom periode.

Metabolic activation of procarcinogenic 2-acetyl-amino-fluorene, benzo(a)pyrene, aflatoxin B1 and N-nitrosodimethylamine by various tissues of embryonal and newborn rats was studied with the Salmonella/microsome assay. Bioactivation by fetal tissues was shown to be significantly lower than with newborn rat tissues. When aroclor was given to pregnant females a decrease in metabolic activation was observed. This phenomenon was interpreted as a paradoxical effect. Treatment with aroclor of newborns led to a significant increase in biotransformation of all the compounds tested in the liver and after benzo(a)pyrene--in the kidney, and N-nitrosodimethylamine--in the lung.

[Phenomenon of enzymatic imprinting in adult animals]. / Fenomen fermentativnogo imprintinga u vzroslykh zhivotnykh.

An inductor of a system of multifunctional monooxygenases, the sovol, being applied to hepatectomized adult rats, produced an enzymatic imprinting, which was expressed in a long-term increase in the aryl hydrocarbon hydroxylase, 7-ethoxycoumarin-deethylase and amidopyrine-N-demethylase activities, as well as in the metabolic activation of benzo (a)-pyrene by the liver S9-fraction in the Salmonella/microsome assay. The phenomena of enzymatic imprinting in adult animals, primarily described, is a reflection of response universality of proliferative cells upon inductors action.