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Solvent Control (solvent + control)
Selected AbstractsEtoposide and merbarone are clastogenic and aneugenic in the mouse bone marrow micronucleus test complemented by fluorescence in situ hybridization with the mouse minor satellite DNA probeENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 2 2003S.M. Attia Abstract The topoisomerase II (topo II) inhibitors etoposide (VP-16) and merbarone (MER) were investigated with the in vivo micronucleus test (MN test) combined with fluorescence in situ hybridization (FISH) using the mouse minor satellite DNA probe to discriminate MN of clastogenic and aneugenic origin. All experiments were performed with male (102/ElxC3H/El) F1 mice bred in the mouse colony of the GSF Research Center. The sample size per experimental group was five animals and 2,000 polychromatic erythrocytes (PCE) were scored per animal from coded slides in the conventional MN test. A separate set of coded slides was used for the FISH analysis. All treatments consisted of single intraperitoneal injections. Colchicine (COL, 3 mg/kg) and mitomycin (MMC, 1 mg/kg) were used as a positive control aneugen and clastogen, respectively, and these compounds produced the expected responses. A dose of 1 mg/kg VP-16 induced 3.44% MNPCE (compared to the concurrent solvent control of 0.37%, P < 0.001) and of these 39.9% (1.4% MNPCE) showed one or more fluorescent signals. MER (7.5,60 mg/kg) increased the MNPCE frequencies in a dose-dependent manner, with 15 mg/kg being the lowest positive dose. At the highest dose of 60 mg/kg of MER, a total of 4.26% MNPCE were found (compared to 0.31% in the concurrent solvent control, P < 0.001) and of these 46.2% (2.0% MNPCE) contained one or more fluorescent signals. The data demonstrate that VP-16 and MER induced both clastogenic and aneugenic events despite their different modes of topo II inhibition. Environ. Mol. Mutagen. 41:99,103, 2003. © 2003 Wiley-Liss, Inc. [source] Enantioselective estrogenicity of o,p'-dichlorodiphenyltrichloroethane in the MCF-7 human breast carcinoma cell line,ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 1 2009Lumei Wang Abstract Research increasingly suggests that selectivity between enantiomers may exist in acute and chronic toxicological effects of chiral contaminants. In this study, we used the human breast carcinoma MCF-7 cell line to evaluate enantioselectivity of o,p'-dichlorodiphenyltrichloroethane (o,p'-DDT). Baseline separation of o,p'-DDT enantiomers was achieved on the Chiralcel® OJ chiral column by high-performance liquid chromatography, and the absolute configuration and optical rotation of the resolved enantiomers were further identified. Significant differences in estrogenic potential were observed between the two enantiomers of o,p'-DDT in the MCF-7 cell proliferation assay (i.e., the E-Screen assay) and the real-time quantitative polymerase chain reaction (PCR). In the E-Screen assay, the relative proliferative effect ratios of R -(,)- o,p'-DDT and S -(+)- o,p'-DDT were 89.4 and 27.9%, respectively, and the relative proliferative potency ratios were 0.1 and 0.001%, respectively. Compared to the solvent control, R -(,)- o,p'-DDT induced the maximal increase of 2.31-fold at a concentration of 10,6 mol/L, while S -(+)- o,p'-DDT at 10,5 mol/L induced the maximal increase of 1.65-fold in estrogenic biomarker pS2 mRNA level. The maximal down-regulation of the transcription levels of estrogen receptor a (ER,) and ER, by R -(,)- o,p'-DDT were 49 and 40% at the concentration of 10,6 mol/L, while those by S -(+)- o,p'-DDT were 24 and 26% at the concentration of 10,5 mol/L. The cell proliferation, the up-regulation of pS2, and the down-regulation of ER, and ER, gene expressions induced by the racemate and enantiomers of o,p'-DDT were all reversed by cotreatment with 10,6 mol/L ICI 182,780. Therefore, the enantioselective estrogenicity of o,p'-DDT was likely through the ER, and ER, signaling pathways. Results from this study suggest the need for considering enantioselectivity of chiral contaminants in chronic ecological toxicities. [source] The joint effects of larval density and 14C-cypermethrin on the life history and population growth rate of the midge Chironomus ripariusJOURNAL OF APPLIED ECOLOGY, Issue 6 2003Helen L. Hooper Summary 1Chemical effects on organisms are typically assessed using individual-level endpoints or sometimes population growth rate (PGR), but such measurements are generally made at low population densities. In contrast most natural populations are subject to density dependence and fluctuate around the environmental carrying capacity as a result of individual competition for resources. As ecotoxicology aims to make reliable population projections of chemical impacts in the field, an understanding of how high-density or resource-limited populations respond to environmental chemicals is essential. 2Our objective was to determine the joint effects of population density and chemical stress on the life history and PGR of an important ecotoxicological indicator species, Chironomus riparius, under controlled laboratory conditions. Populations were fed the same ration but initiated at different densities and exposed to a solvent control and three concentrations of 14C-cypermethrin in a sediment,water test system for 67 days at 20 ± 1 °C. 3Density had a negative effect on all the measured life-history traits, and PGR declined with increasing density in the controls. Exposure to 14C-cypermethrin had a direct negative effect on juvenile survival, presumably within the first 24 h because the chemical rapidly dissipated from the water column. Reductions in the initial larval densities resulted in an increase in the available resources for the survivors. Subsequently, exposed populations emerged sooner and started producing offspring earlier than the controls. 14C-cypermethrin had no effect on estimated fecundity and adult body weight but interacted with density to reduce the time to first emergence and first reproduction. As a result, PGR increased with cypermethrin concentration when populations were initiated at high densities. 4Synthesis and applications. The results showed that the effects of 14C-cypermethrin were buffered at high density, so that the joint effects of density and chemical stress on PGR were less than additive. Low levels of chemical stressors may increase carrying capacity by reducing juvenile competition for resources. More and perhaps fitter adults may be produced, similar to the effects of predators and culling; however, toxicant exposure may result in survivors that are less tolerant to changing conditions. If less than additive effects are typical in the field, standard regulatory tests carried out at low density may overestimate the effects of environmental chemicals. Further studies over a wide range of chemical stressors and organisms with contrasting life histories are needed to make general recommendations. [source] Apple polyphenols diminish the phosphorylation of the epidermal growth factor receptor in HT29 colon carcinoma cellsMOLECULAR NUTRITION & FOOD RESEARCH (FORMERLY NAHRUNG/FOOD), Issue 5 2007Diana Fridrich Abstract Previously, we showed that an apple juice extract (AE) potently inhibits the protein tyrosine kinase (PTK) activity of the epidermal growth factor receptor (EGFR). In the present study, an apple pomace extract (APE) was found to exceed the EGFR inhibitory properties of AE in a cell-free system. The impact of the extracts on the phosphorylation status of the EGFR in intact cells (HT29) was sensitive to catalase, added to suppress the accumulation of hydrogen peroxide. In the absence of catalase, the formation of hydrogen peroxide was observed, achieving 1.1 ± 0.1 ,M (AE) and 1.5 ± 0.1 ,M (APE) after 45 min of incubation. In the presence of catalase, suppressing the hydrogen peroxide level to the solvent control, APE effectively suppressed EGFR phosphorylation, even exceeding the effects of AE. Both extracts inhibited the growth of HT29 cells, albeit the enhanced EGFR inhibitory properties of APE compared to AE were not reflected by a higher growth inhibitory potential. The results clearly show that the effect of apple extracts on the EGFR and cell growth are not simply artefacts of hydrogen peroxide formation. However, the formation of hydrogen peroxide has to be considered to modulate and/or mask cellular responses to apple extracts. [source] Electrophysiological and behavioural identification of host kairomones as olfactory cues for Culicoides impunctatus and C. nubeculosusPHYSIOLOGICAL ENTOMOLOGY, Issue 1 2000A. Bhasin Summary Electroantennograms (EAGs) were recorded from wild-caught parous, female Culicoides impunctatus (Goetghebuer) in response to components of host odour. Nine synthetic compounds were found to be electrophysiologically active, eliciting EAGs which were significantly different from solvent control. An EAG hierarchy was established, in which 1-octen-3-ol elicited the highest amplitude EAGs, followed by acetone, lactic acid and butanone. The overall responses to phenolic compounds were reduced compared to the non-phenolics. Subsequent behavioural analyses of the effects of these compounds when tested singly revealed 1-octen-3-ol, acetone and butanone to be attractive over specific stimulus doses. Exposure to supra-optimal doses modified the insects' behaviour; insects either ceased to respond or were repelled. Lactic acid was attractive at the lowest dose tested but was repellent at high doses. Behavioural responses to the phenolic components of host odour and lactic acid were similar, generally causing arrestment at low doses and repelling at the higher doses tested. A comparison of EAG profiles and behavioural assays between laboratory-reared Culicoides nubeculosus (Meigen) and C. impunctatus suggested that the same kairomones are utilized by both species, with C. nubeculosus being less sensitive than C. impunctatus. The EAG hierarchy of C. nubeculosus to the four non-phenolics was identical to that of C. impunctatus. [source] Inhibition of cyclooxygenase (COX) enzymes by compounds from Daucus carota L. SeedsPHYTOTHERAPY RESEARCH, Issue 8 2003kali A. Momin Abstract Cyclooxygenase (COX) enzymes inhibitory assay directed investigation of Daucus carota seed extracts resulted in the isolation and characterization of compounds, 2,4,5-trimethoxybenzaldehyde (1), oleic acid (2), trans -asarone (3) and geraniol (4). Compounds 1,4 showed 3.32, 45.32, 46.15, and 3.15% of prostaglandin H endoperoxide synthase-I (COX-I) inhibitory activity and 52.69, 68.41, 64.39 and 0% prostaglandin H endoperoxide synthase-II (COX-II) inhibitory activity, respectively at 100 mg mL,1. Compound 1 showed selectivity towards COX-II enzyme inhibition at 100 µg mL,1. The COX-II/COX-I ratio for compound 1 was 17.68 at 100 µg mL,1 compared to solvent control. Ibuprofen, Naproxen, Aspirin, Celebrex and Vioxx at concentrations of 2.06, 2.52, 180, 1.67 and 1.67 µg mL,1, respectively, gave COX-II/COX-I ratios of 1.13, 0.92, 0.24, 16 and 75, respectively. The inhibition of COX-II enzymes by compounds 1 at 100 µg mL,1 was signi,cant when compared to Aspirin, Ibuprofen, Naproxen and Celebrex at concentrations studied. Copyright © 2003 John Wiley & Sons, Ltd. [source] Effect of caffeine on response of rabbit isolated corpus cavernosum to high K+ solution, noradrenaline and transmural electrical stimulationCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 1-2 2004Adebowale Adebiyi Summary 1.,Caffeine has wide-ranging activities on smooth muscles, including contractile and relaxant effects. The aim of the present study was to examine the activity of caffeine on rabbit corpus cavernosum (RCC). 2.,The effects of caffeine (0.5,4.0 mmol/L) on the response of RCC to high K+ solution, noradrenaline (NA) and transmural electrical stimulation (EFS) were studied in a tissue bath system. 3.,Caffeine did not contract the RCC. However, 0.5,4.0 mmol/L caffeine caused concentration-dependent relaxation of tension development in high-K+ (120 mmol/L) solution in contrast with the solvent control. At 4.0 mmol/L caffeine, high-K+ solution-induced tone of the RCC was reduced by 73.4 ± 7.3%. Caffeine (0.5,4.0 mmol/L) also concentration-dependently relaxed NA (12.5 µmol/L)-induced tonic contraction of the RCC. At 4.0 mmol/L caffeine, NA-induced tone of the RCC was reduced by 41.1 ± 7.0%. Incubation of RCC in 2.0 mmol/L caffeine for 30 min prior to EFS (1,40 Hz) caused a marked rightward shift in the frequency,response curve. 4.,The results of the present study suggest that caffeine exhibits relaxant activity on rabbit cavernosal smooth muscle and the mechanism of this activity possibly involves inhibition of Ca2+ signalling. [source] Isocitrate dehydrogenase as a marker of centrilobular hepatic necrosis in the experimental model of rats,JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 3 2001Young-Hwa Chung Abstract Background and Aims: Serum alanine aminotransferase (ALT) and aspartate aminotransferase may not detect centrilobular hepatic necrosis (CLN) of a mild degree because these enzymes are known to be located predominantly in the periportal area. The aim of this study was to evaluate the usefulness of plasma isocitrate dehydrogenase (ICDH), which is located predominantly in the centrilobular zone, as a marker of CLN. Methods: In 56 adult male rats, centrilobular (n = 21) and periportal hepatic necrosis (PPN; n = 21) were induced experimentally by the intraperitoneal injection of bromobenzene and allylalcohol, respectively. Seven rats were used as solvent controls in both groups. Isocitrate dehydrogenase and ALT activities were measured in the plasma of rats with mild to moderate hepatic necrosis (17 CLN and 19 PPN). Isocitrate dehydrogenase and ALT were compared according to the sampling time (12, 24 and 48 h) and the location of hepatic necrosis. Ratios of ICDH/ALT were also calculated and compared between CLN and PPN groups at any time points. Results: Plasma ICDH activities were higher in rats with CLN than in those with PPN. In contrast, plasma ALT levels were higher in rats with PPN than in those with CLN at 12 h and were similar in both groups after 12 h. The ICDH/ALT ratios were much higher in rats with CLN compared to those with PPN (P < 0.001). The ratios were above 1.0 in 13 of 17 rats (77%) with CLN in contrast to none of the 19 rats with PPN. Conclusions: Our data suggested that the plasma ICDH/ALT ratio might be useful to differentiate between mild to moderate degrees of CLN from PPN, at least in the experimental model of rats. [source] | |||||||||||||