Ewa Gregoraszczuk - Academia.edu (original) (raw)

Papers by Ewa Gregoraszczuk

PubMed, Dec 1, 1992

Four types of porcine corpora lutea (CL) were excised at 4 various stages of the luteal phase. On... more Four types of porcine corpora lutea (CL) were excised at 4 various stages of the luteal phase. One part of corpora lutea was homogenized and the concentration of progesterone (P4), estradiol (E2) and androgens (A) was assayed in adequate extracts. Second part of luteal cells obtained from each of four types of CL was cultured as separate monolayers and steroid secretion was measured after 24, 48 and 96 h of culture. The concentration of P4 in homogenates of CL type 2 and 3 was twice as high as that in type 1, while a decrease to minimum level in type 4 was observed. In cultures, maximum increase in P4 production was observed after 24 h, being the highest in type 1 (2800% of initial P4 concentration) and type 2 (320%) while in types 3 and 4 no increase was observed. The contents of androgens (A) in CL homogenates increased 3 times in type 2 and 3 and finally decreased in type 4 as compared with type 1. In cultures, maximum increase in A production was observed after 24 h, being the highest in type 1 (640% of A concentration prior to culture), while in types 2, 3 and 4 it was about 200%. The content of E2 in homogenates of CL types 1 and 2 was very low, but increased to about 200% in type 3 and to about 2500% in type 4.(ABSTRACT TRUNCATED AT 250 WORDS)

Cytotechnology, Sep 30, 2017

Monocultures of different placental cells are used for many physiological and toxicological studi... more Monocultures of different placental cells are used for many physiological and toxicological studies; however, they are not a true reflection of the interaction between placenta and fetus. To develop the most appropriate model to study endocrine and metabolic properties of fetoplacental unit we used three co-culture models of placental cells nonfusogenic JEG-3, unsyncytialised BeWo (BeWo) and syncytialised BeWo (syncBeWo) cultured with adrenal (H295R) cells. As an end point of endocrine properties we investigated steroids receptors expression and steroid secretion, while as metabolic properties AhR, CYP1A1and COMT expression. Progesterone (P4), estradiol (E2) and human chorionic gonadotropin (hCG) secretion (ELISA) and 3bHSD, CYP19, estrogen (ERa/b), progesterone (PR) and aryl hydrocarbon (AhR) receptors, CYP1A1 and COMT protein expression (Western blot) were evaluated. Comparing three co-culture models we observed: (1) there were no differences between JEG-3 and BeWo in the PR expression, however it was higher in BeWo compared to syncBeWo; (2) there were no differences in ERa protein expression in all models, while profile of ERb expression was the highest in syncBeWo; (3) high P4 secretion in JEG-3 and BeWo while low in syncBeWo; (4) high E2 levels in JEG-3 and syncBeWo, while low E2 secretion in BeWo; (5) the highest hCG secretion in the JEG-3 and syncBeWo than in BeWo (6) the highest AhR, CYP1A1 and COMT expression in syncBeWo. Based on the results showing higher hCG secretion in the JEG-3 than in BeWo, representing villous and extravillous phenotype we suggest that JEG-3 model could be used to study fetoplacental steroidogenesis at the 1st, while BeWo model at the 3rd. Results showing comparable profiles of AhR, CYP1A1 and COMT expression in JEG-3 and BeWo models and the significantly higher expression in synBeWo points to synBeWo as a good model for study the metabolic properties.

PubMed, Mar 1, 1983

Porcine granulosa and luteum cells were isolated and cultured in vitro to compare their morpholog... more Porcine granulosa and luteum cells were isolated and cultured in vitro to compare their morphology and secretory activity with these of corpus luteum cells in vivo. Granulosa cells were isolated from preovulatory follicles and the luteal cells were collected from corpora lutea in the early or middle phase of the luteal cycle. The cells were grown as a monolayer for 8 days at 37 degrees C in the Parker's medium (M 199) supplemented with 10% of calf serum. The concentration of progestagens and estrogens in the medium was measured by the radioimmunological method [Abraham et al. 1971, Hotchkiss et al. 1971]. Both granulosa and luteal cells were cultured with the addition of following amounts of hormones: 100 ng LH, 600 ng hCG, 100 ng PRL and 150 ng estradiol per 1 ml of culture medium. At two days of culture the release of progesterone from granulosa cells significantly increased after the addition of 100 ng LH. Luteal cells isolated from the postovulatory corpus luteum released much higher amounts of progesterone than granulosa cells both in control cultures and in cultures supplemented with LH. A secretory stimulation of the luteal cells was observed only on the first day of culture irrespectively of the phase of the luteal cycle. In contrast, granulosa cells reacted by the elevation of hormonal release after the administration of hormones not only at the beginning of the culture, but also after several days. Prolactin did not stimulate the secretory activity of the granulosa cells and the same is valid for the cells isolated from the corpus luteum in the middle luteal phase. However, prolactin stimulated hormonal release of luteal cells isolated from the early corpus luteum.

Journal of Applied Toxicology, Jan 30, 2014

Parabens are alkyl esters of p-hydroxybenzoic acid used widely as antimicrobial preservatives in ... more Parabens are alkyl esters of p-hydroxybenzoic acid used widely as antimicrobial preservatives in consumer products, including pharmaceuticals, foods and cosmetics. We showed previously that methyl-, butyl-and propylparaben parabens, even at low doses, stimulate the proliferation of MCF-7 breast cancer cells and non-transformed MCF-10A breast epithelial cells. The present study was undertaken to determine whether this represents a direct effect on cell cycle and apoptotic gene expression. MCF-7 and MCF-10A cells were exposed to methyl, butyl-and propylparaben (20 nM) or 17βestradiol (10 nM). Cell cycle and apoptotic gene expression were evaluated by real-time polymerase chain reaction and protein expression by Western blot. 17β-estradiol upregulated G 1 /S phase genes and downregulated cell cycle progression inhibitors in both MCF-7 and MCF-10A. Upregulation of Bcl-xL and downregulation of caspase 9 was observed in MCF-7, while upregulation of Bcl-xL, BCL2L2 and caspase 9 was noted in MCF-10A. Cyclins in MCF-7 cells were not affected by any of the parabens. Methyl-and butylparaben had no effect on the expression of selected apoptotic genes in MCF-7. In MCF-10A, all parabens tested increased the expression of G 1 /S phase genes, and downregulated cell cycle inhibitors. Methylparaben increased pro-survival gene. Butylparaben increased BCL2L1 gene, as did 17β-estradiol, while propylparaben upregulated both the extrinsic and intrinsic apoptotic pathways. There are differences in cell cycle and apoptosis gene expression between parabens and 17β-estradiol in MCF-7 cells. In MCF-10A cells, most of the genes activated by parabens were comparable to those activated by 17β-estradiol.

Reproductive Biology and Endocrinology, 2013

Background: Resistin was first reported to be an adipocyte-specific hormone, but recent studies h... more Background: Resistin was first reported to be an adipocyte-specific hormone, but recent studies have indicated a connection between resistin and reproductive function. However, it is not yet known if resistin is expressed by the ovary and if it can affect steroidogenesis in ovarian follicles from prepubertal pigs. Methods: In this study, using real time PCR, immunoblotting, and ELISA, we quantified resistin expression and concentration in maturing ovarian follicles (small, 3-4 mm; medium, 4-5 mm; large, 6-7 mm) collected from prepubertal pigs. In addition, the dose-responsive effects of recombinant human resistin (0.1, 1, 10, and 100 ng/ml) on steroid hormone (i.e., progesterone [P4], androstendione [A4], testosterone [T], and estradiol [E2]) secretion in culture medium and steroidogenic enzyme (i.e., CYP11A1, 3betaHSD, CYP17A1, 17betaHSD, and CYP19A1) expression in ovarian follicles were determined. Results: We observed that resistin gene and protein expression increased significantly (P < 0.05) during follicular growth, with large follicles expressing the highest level of this adipokine. Recombinant resistin also increased P4, A4, and T secretion by up-regulating the steady state levels of CYP11A1, 3betaHSD, CYP17A1, and 17betaHSD. Recombinant resistin had no effects on E2 secretion and CYP19A1 expression in ovarian follicles. Conclusion: Our results show resistin expression in ovarian follicles from prepubertal pigs for the first time. We also show that recombinant resistin stimulates steroidogenesis in ovarian follicles by increasing the expression of CYP11A1, 3betaHSD, CYP17A1, and 17betaHSD. The presence of resistin in the porcine ovary and its direct effects on steroidogenesis suggest that resistin is a new regulator of ovary function in prepubertal animals.

Animal Reproduction Science, Feb 1, 2000

types of cells. In conclusion, the present studies indicate that there are direct and follicular ... more types of cells. In conclusion, the present studies indicate that there are direct and follicular development stage dependent actions of GH on steroidogenesis of porcine follicular cells.

Reproduction, Fertility and Development, 1996

To characterize thyroid hormone action in the ovary, the direct effect of triiodothyronine (T3) w... more To characterize thyroid hormone action in the ovary, the direct effect of triiodothyronine (T3) was investigated in vitro using a culture system of porcine theca cells (Tcs) and granulosa cells (Gcs) in mono-and co-culture (GT), the latter resembling follicles in vivo. The cells were cultured in the absence or presence of human chorionic gonadotrophin (hCG) with or without T3 or lo-" M). Follicular cells were obtained from follicles of different size (small, medium and large), and steroid secretion into the culture medium was detected by radioimmunoassay. T3 alone did not influence steroid secretion by Tcs and Gcs isolated from follicles that were small and medium in size. In preovulatory follicles, an increase in basal androgen secretion and a simultaneous decrease in oestradiol secretion were observed with Tcs and Gcs in both mono-and co-culture. T3 together with hCG decreased hCG-stimulated androgen secretion in Tcs isolated from medium-sized follicles and had a simultaneous stimulatory effect on hCG-stimulated oestradiol secretion by Gcs. In cultures of follicular cells obtained from large follicles, T j decreased hCG-stimulated secretion of both androgen and oestrogen by Tcs and simultaneously stimulated oestradiol secretion in GT co-cultures. Thus, the interaction of T3 with gonadotrophin hormone modulated follicular steroidogenesis, depending on follicle size and cell type used in culture. The observed T3-induced increase in basal androgen secretion by Tcs could account for the atresia of follicles, since it is accompanied by a decrease in oestradiol secretion in GT co-culture. In its co-activity with hCG, an adequate level of T3 prevents excessive androgen production by Tcs, probably influencing aromatization processes in the follicle. An increase in hCG-stimulated oestradiol secretion in GT co-cultures is then observed. Further investigations are required to clarify whether this is linked with an effect on the aromatization processes occurring in the follicle.

Folia Histochemica et Cytobiologica. Supplement, 1997

PubMed, Sep 1, 1998

In the present study hydroxylated cholesterol derivatives were used to monitor P450scc activity a... more In the present study hydroxylated cholesterol derivatives were used to monitor P450scc activity as an effect of triiodothyronine. Luteal cells isolated from mid-developing and mature corpora lutea were plated into 24-well plates by 18 h incubation with M199 supplemented with 5% of alf serum. After that time the plates were washed with fresh M199 and hydroxylated cholesterol derivatives (25-, 20-, and 22-hydroxylated cholesterol) were added to the control (not-T3-treated) and T3-treated cells. Two hours later, all cultures were terminated and the media were frozen until further progesterone analysis. Triiodotyronine added to the culture medium of cells isolated from mature corpora lutea increased both basal and hydroxylated cholesterol derivative-stimulated cells. Aminoglutethimide, a P450scc enzyme inhibitor, added to the culture medium in all doses used, had no effect on basal progesterone secretion while added to the T3-treated cells reduced progesterone production. This study strongly supports the hypothesis of a direct effect of thyroid hormone on mitochondrial cytochrome P450scc--catalysing side-chain cleavage of cholesterol enzyme in luteal cells.

Cancer Chemotherapy and Pharmacology, Aug 31, 2017

two granulosa cancer cell lines: the juvenile form (COV434) and the adult form (KGN). Results ObR... more two granulosa cancer cell lines: the juvenile form (COV434) and the adult form (KGN). Results ObR gene expression in cancer cell lines was 50% higher than in the non-cancer cells. Lan-1 and Lan-2 decreased ObR expression in COV434, while it had no effect in KGN cells. Higher ERβ expression in non-cancer and higher ERα expression in both cancer cell lines was noted. SHLA and Lan-1 changed the ratio towards greater expression of ERβ, characteristic of non-cancer granulosa cells. All ObR antagonists in HCrC1 and KGN but only Lan-2 in COV434 reversed leptin-stimulated proliferation. In both non-cancer and cancer granulosa cells, leptin acts as a cyclinD/cdk4, cyclin A/cdk2 and E2F inhibitor. Conclusion These results indicate that SHLA and Lan2 are promising leptin receptor inhibitors that can eliminate the negative effects of leptin. These compounds should be considered in further ex vivo studies on the cancer microenvironment.

Reproductive Toxicology, Jun 1, 2019

We determined the action of a mixture of 16 priority PAHs present in high concentrations in mater... more We determined the action of a mixture of 16 priority PAHs present in high concentrations in maternal blood (Mix I) and the same but in low concentrations detected in placental tissue (Mix II) on AhR, ERα, NFκB, CYP1A1, CYP1B1, and COMT protein expression and cell proliferation of JEG-3 and BeWo cell lines. Both mixtures induced AhR expression in JEG-3 and BeWo; however, in JEG-3 cells expression of ERα, CYP1A1, CYP1B1, and COMT was upregulated, while in BeWo cells downregulated. The opposite effect of mixtures on NFκB protein expression (inhibitory in JEG-3, stimulatory in BeWo) was noted. We suggest AhR-mediated activation of PAHs metabolism in JEG-3 cells, and AhR interaction with NFκB and AhR cross-talk with ERα causing inhibition of detoxification in BeWo cells. As a result there was a stimulatory effect on JEG-3 and an inhibitory one on BeWo cell proliferation.

PubMed, Aug 1, 2010

Recently, we reported the stimulatory effect of ghrelin on ovarian cell proliferation in parallel... more Recently, we reported the stimulatory effect of ghrelin on ovarian cell proliferation in parallel with the inhibitory action of ghrelin on cell apoptosis. The aim of the presented data propose local activation of extracellular signal-regulated protein kinase 1 and 2 (ERK 1/2) and phosphoinositide-3 (PI-3) kinase pathways as a mechanism of ghrelin effect in the porcine ovary. To test this hypothesis, action of ghrelin on levels of ERK 1/2 with PI-3 kinase activity and protein expression using ELISA and western blot analysis, respectively, was examined. Additionally, to determine which pathways (ERK 1/2 or PI-3 kinase) are the potential signals of ghrelin-mediated cell proliferation and apoptosis in ovarian cells, we used PD098059 (50 microM) and wortmannin (200 microM), well-known inhibitors of these kinases. Treatment of ovarian coculture cells with ghrelin (100, 250, 500 and 1000 pg/ml) showed stimulation of phospho-ERK 1/2 levels and PI-3 kinase activity, with the maximum effect observed after 15 min of cell incubation. Additionally, western blot analysis indicated that ghrelin increased expression of both kinases. Moreover, ghrelin used in combination with PD098059 or wortmannin significantly decreased cell proliferation, which was measured by the Alamar Blue assay and increased apoptosis, which was measured by caspase - 3 activity and DNA fragmentation. In conclusion, these results suggest that the ERK 1/2 and PI-3 kinase pathways may be potential signals of ghrelin mediate the cell proliferation and apoptosis of ovary cells.

PubMed, Sep 1, 2000

To characterize PCB action on follicular cell steroidogenesis two PCB congeners were selected as ... more To characterize PCB action on follicular cell steroidogenesis two PCB congeners were selected as model substances. PCB 126 because of its dioxin-like configuration and high toxicity and PCB 153 because it is one of the most commonly detected PCB congeners in breast milk. The direct effect of PCBs was investigated using a culture system of porcine theca and granulosa cells collected from porcine preovulatory follicles. Granulosa and theca cells were cultured in M199 medium supplemented with 1, 10 or 100 pg/ml of PCB 126 or 1, 10 and 100 ng/ml of PCB 153. The media were changed after 48, 96 and 144 h and frozen until further estradiol (E2) analysis. Additionally, progesterone (P4) was measured in the granulosa cells culture medium and testosterone (T) in theca cells culture medium. Decrease of testosterone concentration in the theca cells culture medium was found after 96 and 144 hours in culture by both investigated PCB congeners. A decrease in E2 concentration was found after exposure to PCB 153. These findings suggest different actions of two congeners on the steroid synthesis in theca cells. The lack of an increase in E2 secretion after the exposure to PCB 126 could be due to depletion of androgen precursor. In granulosa cell culture PCB153 decreased E2 secretion and increased P4 secretion suggesting luteinization and disruption of aromatization process. PCB 126 in a doses from 1 to 10 pg had no effect on granulosa cells steroidogenesis. However, the highest dose (100 pg) increased concentration of both E2 and P4. This observation suggest that PCB 126 in a pharmacological doses may affect cell membrane permeability, thereby increasing steroid outflow into the medium. These results suggest time dependent and cell-specific differences in PCB 153 and 126 action on follicular cells steroidogenesis. Further studies are required to elucidate the mechanism of PCBs action on ovarian steroidogenesis.

Pharmacological Reports, 2011

In the present work, we analyzed whether polybrominated diphenyl ethers (PBDEs) (47, 99, 100 and ... more In the present work, we analyzed whether polybrominated diphenyl ethers (PBDEs) (47, 99, 100 and 209) interfere with the effect of 17b-estradiol on the proliferation and apoptosis of the MCF-7 cell line. MCF-7 cells were cultured in DMEM without phenol red supplemented with 5% charcoal-treated fetal bovine serum for 3 days with 10 nM 17b-estradiol; with 0.1 µM, 0.5 µM or 1 µM of the tested PBDE congeners; or with both 17b-estradiol and a congener. Cell proliferation was determined by measuring BrdU incorporation, and cell apoptosis was measured by caspase-9 activity. No PBDE congener had an effect on basal cell proliferation, but they all significantly decreased basal caspase-9 activity. An additive anti-apoptotic activity and ability to induce cell proliferation was observed in the presence of 17b-estradiol.

Growth hormone & IGF research, Jun 1, 2008

Ghrelin is recognized as an important regulator of growth hormone (GH) secretion, food intake and... more Ghrelin is recognized as an important regulator of growth hormone (GH) secretion, food intake and a factor which controls reproduction. In the present studies, the effect of GH and insulin-like growth factor (IGF-I) on ghrelin synthesis and secretion and the effects of ghrelin on GH synthesis and secretion in cultured whole porcine follicles were studied. Ghrelin and GH levels were measured in the follicular wall and in the culture medium. Moreover, the action of combined treatment with ghrelin and GH on estradiol secretion, aromatase activity and cell apoptosis were examined. We demonstrated that ghrelin increased GH secretion but not GH synthesis by ovarian follicles. GH stimulated both ghrelin synthesis and secretion in the ovarian follicles. The increase in estradiol secretion, aromatase activity and the decrease in caspase-3 activity were noted in ghrelin alone-and ghrelin in combination with GH-treated cells. In culture treated with combination of both these hormones, all investigated parameters were similar to those noted in ghrelin alone-treated cells. In conclusion, our study provides novel evidence for the gonadal feedback loop between GH and ghrelin secretion in the ovary. However, results of the presented research suggest independent action of GH and ghrelin in the ovary.

Endocrine Regulations, 2010

aBDE (BDE-100) are the most dominant which are usually found in wildlife and humans (Meerts et al... more aBDE (BDE-100) are the most dominant which are usually found in wildlife and humans (Meerts et al. 2001). PBDEs are typically produced in three different commercial mixtures, each of them with its own average level of bromination, i.e., penta-PBDE, octa-PBDE, and deca-PBDE mixtures. The commercial penta-PBDE mixture (Bromkal 70-5DE) contains as much as 80 % of only three congeners, i.e. 35 % brominated diphenyl ether (BDE) 47, 38 % of BDE-99 and 7% of BDE-100 (Sjodin et al. 1999). In our recently published data

Cadernos De Saude Publica, Apr 1, 2002

To characterize the action of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) during both the follicul... more To characterize the action of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) during both the follicular and luteal phases of the ovarian cycle, the direct effect of TCDD was investigated in vitro using a system of primary monolayer cell culture. Granulosa and theca cells were collected from the preovulatory follicles and cultured as a co-culture, thus resembling follicles in vivo. Luteal cells were isolated from the corpora lutea collected during the midluteal phase. In both cases cells were isolated from the ovaries of animals exhibiting natural estrus cycle. Results of these experiments suggest that TCDD decreases estradiol secretion by follicular cells and progesterone secretion by luteal cells in a dose-dependent manner. It was also shown that TCDD disrupts steroidogenesis through its influence on the activity of enzymes involved in the steroid biosynthesis cascade. In luteal cells, its action is mediated via the aryl hydrocarbon receptor (AhR) and is probably independent of estrogen receptor (ER) stimulation. Endocrine disruptors that interfere with estradiol production in the follicles can act as ovulatory disruptors, and while interfering with progesterone production by luteal cells they can act as abortifacients.

Reproductive Toxicology, 2008

This study investigated in vitro endocrine disrupting effects of three mixtures of POPs: &amp... more This study investigated in vitro endocrine disrupting effects of three mixtures of POPs: &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;Marine mix&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; extracted from Atlantic cod liver, and two mixtures extracted from burbot liver, &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;Mjøsa mix&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; and &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;Losna mix&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;. The POP mixtures were chemically characterized. Co-culture of theca and granulosa cells, were exposed for 48h with different doses of &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;Marine mix&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;, &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;Mjøsa mix&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; or &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;Losna mix&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;. As an end point cell viability was determinated by LDH test, steroid analysis by EIA and caspase-3 by colorimetric substrate. Chemical characterization of the mixtures demonstrated that the &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;Marine mix&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; contained high levels of DDTs and PCBs. In the &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;Mjøsa mix&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;, the dominant pollutants were BDEs and HBCD. The concentrations of POPs measured in the &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;Losna mix&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; were considerably lower. All mixtures used in the present study had a stimulatory effect on testosterone and estradiol secretion with &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;Marine mix&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;Mjøsa mix&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;Losna mix&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;. These results show that even a mixture containing background concentrations of POPs significantly affected steroid secretion. A higher steroidogenic response in low dose ranges, compared with high dose ranges indicated xenobiotic-conditioning hormesis. This could complicate predictions of effects in risk assessments.

Toxicology, 2019

Polycyclic aromatic hydrocarbons (PAHs) are common environmental pollutants, which are released a... more Polycyclic aromatic hydrocarbons (PAHs) are common environmental pollutants, which are released as products of incomplete combustion processes. Harmful effects of PAHs exposure on human health are observed in increased morbidity of respiratory, cardiovascular

Journal of Applied Toxicology, Sep 2, 2016

Data concerning possible carcinogenic action of polybrominated diphenyl ethers (PBDEs) in hormone... more Data concerning possible carcinogenic action of polybrominated diphenyl ethers (PBDEs) in hormone-dependent tissues are limited. Our earlier studies showed that 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47) stimulated OVCAR-3 and MCF-7 cell proliferation, while its hydroxylated metabolites (5-OH-BDE-47 and 6-OH-BDE-47) increased estrogen receptors protein expression and extracellular signal-regulated kinase 1/2 and protein kinase Cα phosphorylation in these cell lines. In addition to cell proliferative disorder, a failure in the regulation of apoptosis can also lead to the formation and development of tumors. Therefore, in the present study, we investigated the effect of BDE-47 and its metabolites (2.5-50 ng ml-1) on the expression of apoptosis regulatory genes and proteins, caspase-8 and-9 activity and DNA fragmentation induced by extracellular signal-regulated kinase inhibitor (PD098059) and protein kinase Cα inhibitor (Gӧ 6976) in ovarian (OVCAR-3) and breast (MCF-7) cancer cells. In OVCAR-3 cells, BDE-47 upregulated expression of most of the investigated genes and increased protein expression of tumor necrosis factor (TNF)-α, TNF receptor 1, caspase-6, Bcl-xl and caspase-8 activity. Whereas in MCF-7 cells, BDE-47 resulted in the downregulation of most of the investigated genes, and decreased caspase-8 and-9 activity. In both OVCAR-3 and MCF-7 cells, the expression of most of the investigated genes were downregulated by metabolites. Exposure of OVCAR-3 cells to 5-OH-BDE-47 corresponded with a decrease in the protein expression of caspase-6, caspase-9 and Bcl-xl and treatment with 6-OH-BDE-47 decreased Bcl-xl and TNF receptor 1 expression in OVCAR-3 cells and caspase-9 expression in MCF-7 cells. Hydroxylated metabolites of BDE-47 have strong inhibitory effects on apoptosis in ovarian and breast tumor cells and thus should be considered potential carcinogens in hormone-dependent cancers.