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Biomedical subjects

W Körner

Publications and source records attributed to W Körner.

At least 19 recordsLinked to original sources
PubMed2006

Influence of tris(4-chlorophenyl)methanol, non-ortho PCB 77 and gamma-hexachlorocyclohexane on human sperm function in vitro.

In recent years, there has been growing concern that environmental pollutants in general, and organochlorines in particular, adversely affect male fertility. Therefore, we investigated the effects of tris(4-chlorophenyl)methanol (TCPM), non-ortho PCB 77 and gamma-hexachlorocyclohexane (gamma-HCH, lindane) on human sperm functions in vitro. Human spermatozoa from healthy donors were washed in human tubular fluid medium containing 1% human serum albumin, filtered through glass wool and exposed to different concentrations of TCPM, PCB 77 or gamma-HCH. After incubation for 5 h at 37 degrees C and 5% CO(2), sperm vitality and the percentage of living acrosome-reacted spermatozoa were examined using triple stain technique. Total sperm motility was evaluated by computer-assisted sperm analysis (Stroemberg-Mika) after 5 h. For TCPM, total motility was additionally measured after 18 and 40 h. Different concentrations of PCB 77 and gamma-HCH did not alter the percentage of spontaneous living acrosome-reacted spermatozoa, vitality and total motility. TCPM dose-dependently altered sperm motility, vitality and acrosome reaction. The percentage of living acrosome-reacted spermatozoa was increased at overtly toxic concentrations. Therefore, it is suggested that unspecific acrosomal loss has been induced by degenerative processes. In conclusion, even high concentrations of PCB 77 and gamma-HCH did not affect human sperm functions in vitro. Only very high cytotoxic TCPM concentrations modulated spontaneous acrosome reaction and total motility. Therefore, in vivo effects on human sperm function seem to be unlikely. However, individual susceptibility has to be considered and little is known about additive and possible synergistic effects as other environmental pollutants with similar potencies have been found in the human male and female reproductive tract.

Acrosome Reaction↗
PubMed2004

Intrinsic and acquired forms of resistance against the anticancer ruthenium compound KP1019 [indazolium trans-[tetrachlorobis(1H-indazole)ruthenate (III)] (FFC14A).

KP1019 [indazolium trans-[tetrachlorobis(1H-indazole)ruthenate (III)] (FFC14A) is a metal complex with promising anticancer activity. Since chemoresistance is a major obstacle in chemotherapy, this study investigated the influence of several drug resistance mechanisms on the anticancer activity of KP1019. Here we demonstrate that the cytotoxic effects of KP1019 are neither substantially hampered by overexpression of the drug resistance proteins multidrug resistance-related protein 1, breast cancer resistance protein, and lung resistance protein nor the transferrin receptor and only marginally by the cellular p53 status. In contrast, P-glycoprotein overexpression weakly but significantly (up to 2-fold) reduced KP1019 activity. P-glycoprotein-related resistance was based on reduced intracellular KP1019 accumulation and reversible by known P-glycoprotein modulators. KP1019 dose dependently inhibited ATPase activity of P-glycoprotein with a K(i) of approximately 31 microM. Furthermore, it potently blocked P-glycoprotein-mediated rhodamine 123 efflux under serum-free conditions (EC(50), approximately 8 microM), however, with reduced activity at increased serum concentrations (EC(50) at 10% serum, approximately 35 microM). Moreover, P-glycoprotein-mediated daunomycin resistance could only be marginally restored by KP1019 in serum-containing medium, also indicating an influence of serum proteins on the interaction between KP1019 and P-glycoprotein. Acquired KP1019 resistance was investigated by selecting KB-3-1 cells against KP1019 for more than 1 year. Only an approximately 2-fold KP1019 resistance could be induced, which unexpectedly was not due to overexpression of P-glycoprotein or other efflux pumps. Accordingly, KP1019-resistant cells did not display reduced drug accumulation. Their unique cross-resistance pattern confirmed an ABC transporter-independent resistance phenotype. In summary, the likeliness of acquiring insensitivity to KP1019 during therapy is expected to be low, and resistance should not be based on overexpression of drug efflux transporters.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2003

Selective modulation of ER-beta by estradiol and xenoestrogens in human breast cancer cell lines.

In the last decades, substances with estrogenic activity have been dispersed into the environment. Xenoestrogens act by binding to estrogen receptors, ligand-regulated transcription factors, for which two subtypes have been described, ER-alpha and ER-beta, which are often coexpressed at variable amounts in different tissues. We investigated variations in the expression of ER-alpha and ER-beta mRNAs following treatment with four xenoestrogens (bisphenol A, 4-tert octylphenol, 2-hydroxybiphenyl, 4-hydroxybiphenyl) and with 17beta-estradiol in estrogen-sensitive (T47D) and estrogen-insensitive (BT20) breast cancer cell lines. Although to a variable extent, both estradiol and the tested xenoestrogens increased the expression of ER-beta mRNA, whereas a slight effect on ER-alpha was observed only in T47D cells. Upregulation of ER-beta expression by estradiol and xenoestrogens was observed only in the presence of detectable ER-alpha protein levels. These findings indicate a regulatory role for ER-beta in ER-alpha-mediated transcription and a role for ER-beta in mediating xenoestrogen toxicity.

Benzhydryl Compounds↗
PubMed2002

[Competence center for insurance sciences].

The insurance companies located in Hannover have launched an initiative for a "Compentence Center for Insurance Sciences" whose participants include the Hannover Medical School (MHH/HMS), the University of Göttingen and the University of Hannover. A chair of insurance medicine has been established at the MHH/HMS, a professorship for insurance mathematics in Hannover and a professorship for insurance law in Göttingen. In cooperation with the chair of insurance economics, the above-mentioned participants are preparing to open a competence center that will operate as a limited liability company (GmbH), coordinating activities with economic relevance and providing information to encourage interdisciplinary cooperation among the university institutes and the insurance industry.

Curriculum↗
PubMed2002

Estrogenic activity of musk fragrances detected by the E-screen assay using human mcf-7 cells.

The widespread use of synthetic musk fragrances and the resultant presence of these substances and their metabolites in the aquatic environment (as well as their accumulation in human adipose tissue) raises the question of whether musk fragrances display endocrine and in particular estrogenic activity. A variety of musk fragrances were tested using the E-screen assay. A statistically significant increase in proliferation rate of human MCF-7 breast cancer cells was detected for two nitro musks (musk xylene, musk ketone), a major metabolite of musk xylene ( p-amino-musk xylene), and the polycyclic musk fragrance AHTN. This indicates that these substances do, in fact, demonstrate estrogenic activity. Coincubation with the antiestrogen tamoxifen showed that the increase in proliferation rate by the musk fragrances is estrogen receptor-mediated. It must be noted, however, that the effective estrogenic strength and estrogenic potency were low compared to 17 b-estradiol. The naturally occurring fragrance muscone from the group of macrocyclic musk fragrances, a group of substances that have not yet been well characterized in respect to their toxicological properties, has also been shown to be weakly estrogenically active in vitro. E-screen analysis showed that the nitro musk metabolites o-amino musk xylene and 2-amino-MK, the macrocyclic musk fragrances ethylene brassylate, ethylene dodecandioate, and cyclopentadecanolide, are not estrogenically active.

Biological Assay↗
PubMed2001

Phenolic xenoestrogens in surface water, sediments, and sewage sludge from Baden-Württemberg, south-west Germany.

Nine structurally different phenolic chemicals, which have been reported to mimic estrogen effects, were determined in various aquatic environmental compartments. Twenty-three water samples from five streams and rivers showed levels up to 458 ng/l for 4-nonylphenol (4NP), 189 ng/l for 4-t-octylphenol (4tOP), 272 ng/l for bisphenol A (BPA) and 47 ng/l for 2-hydroxybiphenyl (2OHBiP). Elevated levels of these compounds in a stream with a high load of effluents of sewage treatment plants (STPs), compared to a brook free of sewage, identified STPs as major sources. With a similar order, 4NP (10-259 micrograms/kg dry matter), 4tOP (< 0.5-8 micrograms/kg), BPA (< 0.5-15 micrograms/kg), and 2OHBiP (2-69 micrograms/kg) were also detected regularly in riverine sediment (n = 11). Levels in sewage sludge were one order of magnitude higher than in sediments. 4-Hydroxybiphenyl and 4-chloro-3-methylphenol were found predominantly in sludge and sediment in the lower ppb range.

Estrogens, Non-Steroidal↗
PubMed2001

Application of the E-screen assay to test for oestrogenically active substances in swine feed.

A pig breeder in central Hesse (Germany) noticed the occurrence of enlarged vulvae in female piglets. Intoxication with oestrogenically active substances by contamination of two feed mixes ingested by the mother sows appeared to be a possible cause. Using a combined technique of the DFG analytical method S19 and the E-screen assay, two feed samples were found to contain powerful oestrogenically active compounds. By co-incubation with the anti-oestrogen tamoxifen it could be clearly demonstrated that the oestrogenic activity was mediated by the oestrogen receptor. These results demonstrate that use of the E-screen assay in combination with the DFG analytical method S19 provides a simple and readily usable prescreening method for the routine detection of oestrogenically active compounds in animal feed. The results from the E-screen assay show that the sows ingested 10-80 microg oestradiol equivalents per day in their feed. Because of the bioavailability of these substances, the oestrogenic active compounds seem to be transferred into the milk and passed to the piglets via suckling. The milk of the dam appears to contain this substance in biologically active form and at such high concentrations that the female piglets had enlarged vulvae.

Animal Feed↗
PubMed2001

Substances with estrogenic activity in effluents of sewage treatment plants in southwestern Germany. 1. Chemical analysis.

A gas chromatography/mass spectrometry method for the simultaneous quantitative determination of natural and synthetic estrogens (17beta-estradiol, estrone, 17alpha-ethinylestradiol, and mestranol), phytoestrogens (genistein and beta-sitosterol), and xenoestrogens (benzyl butyl phthalate, dibutyl phthalate, bisphenol A, 4-nonylphenol [NP], 4-nonylphenoxyacetic acid [NP1EC], 4-nonylphenol diethoxylate [NP2EO], and alpha-endosulfan) in effluents of sewage treatment plants (STPs) was developed. Identification and quantification were carried out with the standard addition method using analyte-specific and, in some cases, deuterium-labeled internal standards. The effluents of 18 STPs were investigated. Apart from alpha-endosulfan and mestranol, all selected substances were detected in the majority of samples. The median concentrations of steroidal estrogens were between 0.4 ng/L (17alpha-ethinylestradiol) and 1.6 ng/L (17beta-estradiol). The metabolites of the nonylphenol polyethoxylates, NP, NPIEC, and NP2EO were found in concentrations ranging from the upper-ng/L-range (NP) to the lower-microg/L range (NP1EC). For all substances except mestranol and alpha-endosulfan, median values were calculated and compared to the results of other investigations in Europe and the United States. Possible dependencies of measured concentrations on the geographical location, the capacity, the influent composition, and the technical fitting of the STPs are discussed.

Charcoal↗
PubMed2001

Substances with estrogenic activity in effluents of sewage treatment plants in southwestern Germany. 2. Biological analysis.

The proliferation test with human estrogen receptor-positive MCF-7 breast cancer cells (E-Screen assay) was applied for quantitative determination of total estrogenic activity in 24-h composite effluent samples from 16 municipal and two industrial sewage treatment plants (STPs) in the state of Baden-Württemberg, southwestern Germany. The estrogenic efficacy relative to the positive control, 17beta-estradiol, was between 26 and 74% (median, 48%) for the 16 municipal STPs. Estradiol equivalent concentrations (EEQs) were between 0.2 and 7.8 ng/L (median, 1.6 ng/L) and, thereby, were lower than those found in a pilot study, which revealed EEQs of greater than 10 ng/L in the effluents of two other STPs. The EEQs in 14 of the 16 effluent samples were very similar (0.9-3.3 ng/L), indicating a rather constant input of estrogenic substances via STPs into rivers. Additional activated charcoal filtration turned out to be very efficient in further eliminating estrogenic activity from effluents. The EEQs of the E-Screen assay and those calculated from the results of extensive chemical analysis using the estradiol equivalency factors determined for 13 natural and synthetic estrogenic substances were comparable for most of the effluent samples. 17beta-Estradiol, 17alpha-ethinylestradiol, and, to a lesser extent, estrone contributed to 90% or more of the EEQ value.

Charcoal↗
PubMed2000

Identification and quantification of estrogenic compounds in recycled and virgin paper for household use as determined by an in vitro yeast estrogen screen and chemical analysis.

The use of recycled paper for the manufacture of food contact materials is widespread, but very little is known about the presence of potential contaminants in the paper. The purpose of this study was to assess the worst-case migration of estrogenic active compounds using extracts of paper for household use. Twenty different brands of kitchen rolls, nine of which were made from recycled paper and the remainder from virgin paper, were obtained from retail shops. Paper extracts were subjected to (a) determination of the total estrogenic activity by using an in vitro estrogen screen based on yeast cells stably transfected with the human estrogen receptor alpha and (b) chemical analysis and quantification by GC/MS, GC/FTIR/MS, and GC/FID for detection of a variety of estrogenic compounds. A marked estrogenic response was observed in nine of the extracts, seven of which were made from recycled paper and two from virgin paper. The chemical analysis revealed that extracts made from recycled paper contained levels of bisphenol A ranging from 0.6 to 24 mg/kg of kitchen roll, whereas extracts from virgin paper contained no bisphenol A or only negligible amounts. In contrast, 4-tert-octylphenol, 4-nonylphenols, and di-n-butyl and diisobutyl phthalate were present to a varying degree in both recycled and virgin paper with no apparent preferable distribution between the two paper types. The estrogenic response of the two extracts made from virgin paper appeared to be due partly to the presence of the preservative propyl paraben. Diisopropylnaphthalene, which turned out to be weakly estrogenic active in vitro (EC(50) = 53 microM), was detected in minor amounts in most of the extracts with the major part, ranging from 0.3 to 4.7 mg/kg of paper, found in recycled paper. Our findings that recycled kitchen rolls contain bisphenol A and other xenoestrogens may apply to other types of recycled paper used for food packaging and emphasize the importance of identifying this and other contaminants in recycled paper in general. These data indicate that bisphenol A may be useful as a purity indicator for recycled paper.

Benzhydryl Compounds↗
PubMed1999

Development of a sensitive E-screen assay for quantitative analysis of estrogenic activity in municipal sewage plant effluents.

A simplified proliferation test with human estrogen receptor-positive MCF-7 breast cancer cells (E-screen assay) was optimized and validated for the sensitive quantitative determination of total estrogenic activity in effluent samples from municipal sewage plants. After solid phase extraction of 1 l sewage on either 0.2 g polystyrene copolymer (ENV+) or 1 g RP-C18 material and removal of the solvent, analysis of the extracts in the E-screen assay could be performed without any clean-up step. This was even possible with untreated sewage. Parallel extraction of four sewage samples on both different solid phase materials gave comparable quantitative results in the E-screen. A blank sample did not induce cell proliferation. As additive behaviour of the estrogenic response of single compounds was proven for two different mixtures each containing three xenoestrogens, total estrogenic activity in the sewage samples, expressed as 17 beta-estradiol equivalent concentration (EEQ), could be calculated comparing the EC50 values of the samples with those of the positive control 17 beta-estradiol. The detection limit of the E-screen method was 0.05 pmol EEQ/l (0.014 ng EEQ/l), the limit of quantification 0.25-0.5 pmol EEQ/l (0.07-0.14 ng EEQ/l). In total, extracts of nine effluent and one influent sample from five different municipal sewage plants in South Germany were analyzed in the E-screen. All samples strongly induced cell proliferation in a dose-dependent manner which was completely inhibited by coincubation with 5 nM of the estrogen receptor-antagonist ICI 182,780. The proliferative effect relative to the positive control 17 beta-estradiol (RPE) was between 30 and 101%. 17 beta-Estradiol equivalent concentrations were between 2.5 and 25 ng/l indicating a significant input of estrogenic substances via sewage treatment plants into rivers.

Biological Assay↗
PubMed1996

Tissue distribution after a single subcutaneous administration of 2,3,7,8-tetrabromodibenzo-p-dioxin in comparison with toxicokinetics of 2,3,7,8-tetrachlorodibenzo-p-dioxin in female Wistar rats.

Tissue concentrations of 2,3,7,8-tetrabromodibenzo-p-dioxin (TBDD) and induction of ethoxyresorufin O-deethylase (EROD) were determined in female Wistar rats following a single subcutaneous (s.c.) injection of TBDD. Two sets of experiments were performed in order to study (a) the time course after a single s.c. administration of 600 ng TBDD/kg body wt up to 78 days, and (b) the dose-response seven days after a single s.c. injection of different doses of TBDD (3 to 3,000 ng/kg body wt). The results obtained on toxicokinetics and enzyme induction were compared with those following a single s.c. administration of 300 ng/kg body wt 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Three days after the injection, approximately 93% of TBDD and 90% of TCDD had been absorbed. Fourteen days after s.c. injection less than 1% of the administered dose of both substances remained at the injection site. Three days after a single s.c. injection of 600 ng TBDD/kg body wt and 300 ng TCDD/kg body wt, the maximum tissue concentrations in the liver amounted to (M +/- S.D.) 5.7 +/- 0.8 and 4.7 +/- 0.9 ng/g wet weight, respectively. In adipose tissue, the peak concentration was 3.2 +/- 0.2 ng/g wet weight for TBDD on day 14, and 0.8 +/- 0.1 ng/g for TCDD on day 7. Throughout the study, the concentration ratio in the TCDD-treated group was always at least twice as high as that in the TBDD-treated group. The elimination half-life (t1/2) of TBDD and of TCDD in the liver was 13.3 and 13.6 days, respectively. In the adipose tissue the t1/2 of TCDD was 24.5 days but no reliable t1/2 could be calculated for TBDD (t1/2 = 39.4 days with a 95% confidence interval of 25.9 to 82.4 days). Tissue content of TBDD and TCDD in liver and adipose tissue increased dose-dependently, and the linear regression in a double-logarithmic plot showed a straight line. Time course of the induction of hepatic EROD activity after treatment with 600 ng TBDD/kg body wt was almost identical with that observed following a single dose of 300 ng TCDD/kg body wt. The induction of hepatic EROD activity was linearly correlated in a double-logarithmic plot to the hepatic concentrations of the congeners (both TBDD and TCDD). The slopes of the dose-response curves after administration of TBDD and TCDD were almost parallel for tissue concentrations ranging from 0.1 to 30 ng/g wet weight.

Absorption↗
PubMed1994

Effects of 2,3,7,8-tetrachloro- and 1,2,3,4,6,7,8-heptachlorodibenzo-p-dioxin on the proliferation of preneoplastic liver cells in the rat.

Using an initiation-promotion system, enzyme-altered putative preneoplastic liver foci were induced in female Wistar rats by application of diethylnitrosamine (10 mg/kg/day) for 5 days, followed by bi-weekly treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; corresponding to 100 ng/kg/day) or 1,2,3,4,6,7,8-heptachlorodibenzo-p-dioxin (HCDD; corresponding to 5 micrograms/kg/day) for up to 17 weeks. Groups of animals were killed at various time intervals after start of promoter treatment. For evaluation of DNA synthesis, 5-bromo-2'-deoxyuridine was administered 24 h prior to killing the animals. Quantitative analysis of the number and volume fraction of adenosine-triphosphatase-deficient liver foci revealed that the promoting activity of both dioxins was roughly comparable under the experimental conditions employed. Nuclear labelling indices (LIs) of normal hepatocytes were not altered by TCDD or HCDD treatment, while a slight increase in LIs of non-parenchymal liver cells was observed. Using an immunohistochemical double-staining technique, hepatocytes within glutathione-transferase P-positive liver foci were found to show an approximately 5-to 10-fold higher LI than normal hepatocytes throughout all periods of investigation. During the time course of the experiment, LIs of foci from all treatment groups decreased with time. However, in TCDD-treated rats, and less pronounced in HCDD-treated rats, the initially high rate of proliferation persisted for a greater length of time than in non-dioxin-treated control animals. Assignment of liver foci into four transection size classes revealed that LIs in larger size classes varied considerably, indicating heterogeneity in the growth behaviour of individual liver lesions. Overall, both dioxins had no effects on the proliferation of normal hepatocytes, while LIs of enzyme-altered liver lesions were slightly enhanced by treatment with TCDD or HCDD. Whether the selective, albeit moderate increase in the proliferation of enzyme-altered liver cells is sufficient to explain the promoting activity of dioxins, or if additional factors (e.g. decrease in death rates of foci cells) are equally important, remains to be determined in further experiments.

Animals↗
PubMedDate not supplied

Concentrations and profiles of PCDDs and PCDFs in human mammary carcinoma tissue.

PCDD/PCDF concentrations in eight mammary carcinoma tissue samples obtained after surgical excision were similar to those found in two healthy breast glandular tissue samples from autopsy material. These levels agree well with mean concentrations in human adipose tissue from German adults. An analogous consistency was found for the congener profiles of the normalized concentrations, also in comparison with mothers' milk from Germany. In spite of similar congener profiles the concentrations in four axillary adipose tissue samples corresponding to the carcinoma samples were about 40% lower. This discrepancy was not found in one tissue pair from a healthy breast.

Adipose Tissue↗