Degradation of Polychlorinated Biphenyls by UV-Catalyzed Photolysis

Photolysis of five polychlorinated biphenyl (PCB) congeners [2,4,4′-trichlorobiphenyl (PCB 28), 2,2′,5,′5-tetrachlorobiphenyl (PCB 52), 2,2′,4,5,5′-pentachlorobiphenyl (PCB 101), 2,2′,4,4′,5,′5-hexachlorobiphenyl (PCB 153) and 2,2′,3,4,4′,5,′5-heptachlorobiphenyl (PCB 180)] individually and in combination were carried out in the solvents methanol, ethanol, and 2-propanol. The disappearance of parent congener generally increased with UV intensity. The solvents had significant or limited effect on the removal of PCBs depending on the congener used. Because 2-propanol was highly toxic and methoxylated products were formed when methanol was used, ethanol was selected as the optimum solvent. The results of photolysis of the PCB mixture showed that PCB 52 was formed and accumulated after 4 h of photolysis. The addition of sodium hydroxide increased the rate of photolysis of the PCB mixture. One hundred percent removal can be obtained of the PCB in mixture in 90 min under optimized conditions. Gas chromatography–mass spectrometry was used to determine the intermediates of the photolysis of PCBs under optimized conditions. For the PCB congeners and mixture studied, the major photolytic intermediates were less chlorinated congeners, and biphenyl was the major product with minor amounts of hydroxylated PCBs, ethylated, dimethylated, and methylated biphenyls. Biphenyl could be further degraded by a prolonged photolysis. Toxicity of the PCB mixture during photolysis was monitored by the Microtox^® test. It was found that the toxicity increased at the early stage of photolysis, and gradually decreased as the reaction proceeded. After 90 min, the EC₅₀ of the reaction mixture was similar to that of the untreated sample.     

Interaction of benzo[a]pyrene, 2,3,3′,4,4′,5 hexachlorobiphenyl (PCB 156) and cadmium on biomarker responses in flounder (Platichthys flesus L.)

Interactive effects of a mixed pollutant exposure on biomarker responses were studied in European flounder (Platichthys flesus L.). The model chemicals, benzo[a]pyrene (BaP, 2.5 mg kg^-1), 2,3,3′,4,4′5 hexachlorobiphenyl (PCB-156, 2.5 mg kg^-1), and cadmium (cadmium, 1 mg kg^-1), were administered to fish by subcutaneous injections. Biomarker responses were quantified both following administration of single chemicals and sequential combinations of the chemicals in pairs. Significant induction of CYP1A protein levels and corresponding ethoxyresorufin-O-deethylase (EROD) activities was observed in BaP and PCB treated flounder after 2 and 8 days, respectively. The strongest induction (44 fold) was caused by BaP. No further induction was observed after additional treatment with PCB 156. CYP1A induction caused by BaP was inhibited (40% compared with BaP treatment alone) in flounder pre treated with cadmium, whereas induction by PCB 156 appeared to be unaffected by pre treatment with cadmium. Flounder treated with cadmium only had significantly elevated hepatic levels of metallothionein (MT) after 15 days. Pre treatment with BaP and PCB prior to cadmium inhibited the MT induction (30-50%) compared with cadmium alone. Furthermore, significantly higher glutathione S transferase activities were observed in flounder administered cadmium alone, and in flounder treated with BaP or PCB 156 prior to cadmium. GST selenium independent peroxidase activities appeared to be unaffected by any of the treatments in the present study. The results indicate that chemical mixtures may affect biomarker responses differently from compounds administered alone, and that the sensitivity of both CYP1A and MT are influenced by pollutants other than their primary inducers.     

Exposure to polychlorinated biphenyls causes endothelial cell dysfunction

Environmental chemicals, such as polychlorinated biphenyls (PCBs), may be atherogenic by disrupting normal functions of the vascular endothelium. To investigate this hypothesis, porcine pulmonary artery-derived endothelial cells were exposed to 3,3′,4,4′-tetrachlorobiphenyl (PCB 77), 2,3,4,4′,5-pentachlorobiphenyl (PCB 114), or 2,2′,4,4′,5,5′-hexachlorobiphenyl (PCB 153) for up to 24 hours. These PCBs were selected for their varying binding avidities with the aryl hydrocarbon (Ah) receptor and differences in their induction of cytochrome P450. PCB 77 and PCB 114 significantly disrupted, in a dose-dependent manner, endothelial barrier function by allowing an increase in albumin transfer across endothelial monolayers. These PCBs also contributed markedly to cellular oxidative stress, as measured by 2,7-dichlorofluorescin (DCF) fluorescence and lipid hydroperoxides, and caused a significant increase in intracellular calcium ([Ca²⁺]_i) levels. Enhanced oxidative stress and [Ca²⁺]_i in PCB 77- and PCB 114-treated cells were accompanied by increased activity and content of cytochrome P450 1A and by a decrease in the vitamin E content in the culture medium. In contrast to the effects of PCB 77 and PCB 114, cell exposure to PCB 153 had no effect on cellular oxidation, [Ca²⁺]_i, or endothelial barrier function. These results suggest that certain PCBs may play a role in the development of atherosclerosis by causing endothelial cell dysfunction and a decrease in the barrier function of the vascular endothelium. It is possible that interaction of PCBs with the Ah receptor and activation of the cytochrome P450 1A subfamily are involved in this pathology. © 1995 John Wiley & Sons, Inc.     

Synthesis and biological evaluation of 3′,4′,5′-trimethoxychalcone analogues as inhibitors of nitric oxide production and tumor cell proliferation

A series of 23 3′,4′,5′-trimethoxychalcone analogues was synthesized and their inhibitory effects on nitric oxide (NO) production in LPS/IFN-γ-treated macrophages, and tumor cell proliferation has been investigated. 4-Hydroxy-3,3′,4′,5′-tetramethoxychalcone (7), 3,4-dihydroxy-3′,4′,5′-trimethoxychalcone (11), 3-hydroxy-3′,4,4′,5′-tetramethoxychalcone (14), and 3,3′,4′,5′-tetramethoxychalcone (15) were the most potent growth inhibitory agents on NO production, with an IC₅₀ value of 0.3, 1.5, 1.3 and 0.3 μM, respectively. The tumor cells proliferation assay results revealed that several compounds exhibited potent inhibition activity against different cancer cell lines. The chalcone 15 was the most potent anti-proliferative compound in the series with IC₅₀ values of 1.8 and 2.2 μM toward liver cancer Hep G2 and colon cancer Colon 205 cell lines, respectively. 2,3,3′,4′,5′-Pentamethoxychalcone (1), 3,3′,4,4′,5,5′-hexamethoxychalcone (3), 2,3′,4,4′,5,5′-hexamethoxychalcone (5), 2-hydroxy-3,3′,4′,5′-tetramethoxychalcone (10), 11 and 14 showed significant anti-proliferation actions in Hep G2 and Colon 205 cells with an IC₅₀ values ranging between 10 and 20 μM. Among the tested agents, compound 7 showed selective NO production inhibition (IC₅₀ = 0.3 μM), while has no effect on tumor cell proliferation (IC₅₀ >100 μM). 3,3′,4,4′,5′-Pentamethoxychalcone (2) showed selective anti-proliferation effect in Hep G2 cells, in addition to its potent NO inhibition, however has no such response in Colon 205 cells. In contrast, 3-formyl-3′,4′,5′-trimethoxychalcone (22) showed moderate growth inhibition in Colon 205 cells, while has no such effect on NO production and Hep G2 cells proliferation. These results provide insight into the correlation between some structural properties of 3′,4′,5′-trimethoxychalcones and their in vitro anti-inflammatory and anti-cancer differentiation activity.     

Bicyclo[3,2,1]octanoid,neolignans from Aniba simulans

Six bicyclo[3,2,1]octanoid neolignans, isolated from the benzene extract of Aniba simulans Allen (Lauraceae) trunk wood, are shown to derive from two basic structures: 1-allyl-8-hydroxy-6-(3′-methoxy-4′,5′-methylenedioxyphenyl)-7-methyl-3-oxobicyclo[3,2,1]octane, substituted by 4-hydroxy, 4-hydroxy-5-methoxy, 4-methoxy or 4,5-dimethoxy groups; and 1-allyl-8-hydroxy-6-(3′-methoxy-4′,5′-methylenedioxyphenyl)-7-methyl-4-oxobicyclo[3,2,1]oct-2-ene, substituted by 3-hydroxy or 3-hydroxy-5-methoxy groups. The structural proposals are based on spectral data, interconversions synthesis of a derivative from the known (2R,3S,3aS)-3a-allyl-5-methoxy-2-(3′-methoxy,4′,5′-methylenedioxyphenyl)-3-methyl-2,3,3a,6-tetrahydro-6-oxobenzofuran.     

Induction of both cytochromes P-450 and P-448 by 2,3',4,4',5-pentabromobiphenyl, a component of fireMaster

The synthesis and purification of a component of fireMaster BP-6 and fireMaster FF-1, 2,3′,4,4′,5-pentabromobiphenyl, is described. The compound was found to be a potent inducer of liver microsomal drug-metabolizing enzymes in the rat, enhancing those enzymic activities induced by both phenobarbitone and 3-methylcholanthrene (i.e. cytochromes P-450 and P-448). The pentabromobiphenyl enhanced the activities of benzo[a]pyrene hydroxylase, dimethylamino-antipyrine N-demethylase and NADPH-cytochrome c reductase. The hepatic cytochromes b₅ and P-450 were increased and the Soret peak maximum of the latter was shifted to 448.5 nm. The relative peak intensities and spectral shifts for the ethylisocyanide-binding difference spectra confirmed the mixed induction characteristics of 2,3′,4,4′,5-pentabromobiphenyl.     

Synthetic Nucleosides and Nucleotides. XXX.1 Synthesis and Antiviral Activity of 3′-Azido, 2′,3′-Unsaturated and 2′,3′-Dideoxy Derivatives of E-5-Styryl-2′-Deoxyuridine on Human Immunodeficiency Virus

Abstract

Some new 3′-azido, 2′,3′-unsaturated and 2′,3′-dideoxy 5-styryl analogs of deoxyuridine-related compounds have been synthesized and evaluated against human immunodeficiency virus in vitro. Among these compounds, 3′-azido-2′,3′-dideoxy-5-E-styryluridine (6) and 2′,3′-dideoxy-E-5-styryluridine (9) were found to be active, with ED₅₀ values of 5 and 10 μg/ml respectively.     

Nonadditive interactive effects of polychlorinated biphenyl congeners in rats: role of the 2,3,7,8-tetrachlorodibenzo-p-dioxin receptor

Administration of 3,3',4,4',5,5'-hexa-,3,3',4,4',5-penta-, and 2,3,3'4,4'5-hexa-chlorobiphenyl to immature male Wistar rats caused a thymic atrophy at high dose levels (1.25, 1.0, and 100 mumol/kg, respectively) and induced the hepatic cytochrome P-448 dependent monooxygenases (benzo[a]pyrene hydroxylase and ethoxyresorufin O-deethylase) at both high and low (0.25, 0.01, and 5 mumol/kg, respectively) doses. In contrast, 2,2',4,4',5,5'-hexachlorobiphenyl (HCBP) (300 mumol/kg) did not elicit any of these effects but elevated hepatic 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) cytosolic receptor protein levels (threefold) as previously reported. The effects of hepatic receptor modulation by 2,2',4,4',5,5'-HCBP (300 mumol/kg) on the enzyme induction activities of 3,3'4,4',5-penta-, 3,3'4,4',5,5'-hexa-, and 2,3,3',4,4',5-hexa-chlorobiphenyl were dose-dependent; no interactive effects were observed at high (toxic) doses of these compounds, whereas apparent synergistically increased hepatic microsomal monooxygenase induction activities were noted at the lower submaximal induction doses. It was concluded that the increased responsiveness of the rats was due to elevated hepatic 2,3,7,8-TCDD receptor levels.     

Polychlorinated biphenyl isomers and congeners as inducers of both 3-methylcholanthrene- and phenobarbitone-type microsomal enzyme activity

Highly purified synthetic polychlorinated biphenyls substituted in the meta and para positions of both phenyl rings and at one ortho position were administered to male Wistar rats and the effects of these compounds on the microsomal drug-metabolising enzymes were evaluated. The in vivo effects of these compounds were determined by measuring the microsomal benzo[a]pyrene hydroxylase, dimethylaminoantipyrine N-demethylase and NADPH-cytochrome c reductase enzyme activities, the cytochrome b5 content and the relative peak intensities and spectral shifts of the reduced microsomal cytochrome P-450 : CO and ethylisocyanide binding difference spectra. The results were compared to the effects of administering phenobarbitone (PB), 3-methylcholanthrene (MC), 2,2',4,4'-tetrachlorobiphenyl (TCBP-II) (a PB-type inducer), 3,3',4,4'-tetrachlorobiphenyl (TCBP-I) (an MC-type inducer), PB plus MC (coadministered) and TCBP-II + TCBP-I (coadministered) to the test animals. At dosage levels of 30 and 150 mumol . kg-1, pretreatment with 2,3,3',4,4'-pentachlorobiphenyl (PCBP-II), 2,3',4,4',5-pentachlorobiphenyl (PCBP-I), 2,3,3',4,4',5-hexachlorobiphenyl (HCBP-II) and 2,3,3',4,4',5-hexachlorobiphenyl (HCBP-III) gave hepatic microsomes with enzymic and spectral properties consistent with a mixed pattern of induction. These polychlorinated biphenyl (PCB) isomers and congeners have been identified as either major or minor components of the commercial PCB mixtures and must contribute to their activity as MC-type inducers. The only PCB isomer in this series which was not a mixed type inducer was 2,3',4,4',5,5'-hexachlorobiphenyl (HCBP-I) which appeared to be a PB-type inducer. This contrasted to the mixed-type activity observed for 2,3',4,4',5,5'-hexabromobiphenyl which was isolated from a commercial polybrominated biphenyl (PBB) mixture.     

Urinary ascorbic acid—HPLC determination and application as a noninvasive biomarker of hepatic response

A high-performance liquid chromatograph (HPLC) procedure has been developed for the determination of rat urinary ascorbic acid, a major metabolite cf the hepatic glucuronic acid pathway. The presence of EDTA and HC1 effectively inhibited degradation of ascorbic acid during the collection of urine specimens. The reliability of the procedure was demonstrated by its high recovery (90%), specificity (characteristic absorption maximum and discrimination from iso-ascorbic acid), and reproducibility (2–3% coefficient of variation). The usefulness of this assay as an indicator of hepatic response was demonstrated in preliminary experiments where increases in urinary ascorbic acid excretion were detected in male rats treated with PCB 126 (3,3′,4,4′,5-pentachloro-biphenyl) or PCB 105 (2,3,3′,4,4′-pentachlorobi-phenyl). The HPLC measurement also showed that the two PCB congeners differed markedly in their potency in stimulating urinary ascorbic acid excretion. For example, 10 μ/kg bw/day of PCB 126 was sufficient to cause a fourfold increase in urinary ascorbic excretion while 5000 μ/kg bw/day of PCB 105 was required for a sevenfold increase. In response to the administration of PCB 105 or PCB 126, urinary ascorbic acid appeared to increase to the same extent as increases in hepatic ethoxyresorufin O-deethylase (EROD) and UDP-glucuronosyltransferase (UGT) activities, and to a much higher extent than changes in liver weight and hematological and serum clinical chemical parameters. The sensitivity and specificity, the ease in obtaining timed specimens, and the noninvasive nature make this assay a useful biomarker of hepatic response in dose-finding and various acute and chronic studies.     

Eusiderins and other neolignans from an Aniba species

A previous report disclosed the presence of benzodioxan and bicyclo[3.2.1]octanoid neolignans in the benzene extract of the trunk wood of an Amazonian Aniba (Lauraceae) species. The chloroform extract of the same material contains additionally two new benzodioxan neolignans [rel-(7S,8R)-Δ^8′-7-hydroxy-3,4,5,5′-tetramethoxy-7.0.3′,8.0.4′-neolignan; rel-(7R,8R)-Δ^7′-3,4,5,5′-tetramethoxy-9′-oxo-7.0.3′,8.0.4′-neolignan], two new bicyclo[3.2.1]-octanoid neolignans [(7R,8S,1′S,2′S,3′S,4′R)-Δ^8′-2′,4′-dihydroxy-3,3′-dimethoxy-4,5-methylenedioxy-1′,2′,3′,4′,5′,6′-hexahydro-5′-oxo-7.3′,8.1′-neolignan; (7R,8S,1′R,2′S,3′S)-Δ^8′-2′-hydroxy-3,3′,5′-trimethoxy-4,5-methylenedioxy-1′,2′,3′,4′-tetrahydro-4′-oxo-7.3′,8.1′-neolignan] and a hydrobenzofuranoid neolignan [(7S,8R,1′S,5′S)-Δ^8′-3,3′,5′-tri-methoxy-4,5-methylenedioxy-1′,4′,5′,6′-tetrahydro-4′-oxo-7.0.2′,8.1-neolignan].     

Reaction of methanesulphonyl chloride-N,N-dimethylformamide with partially esterified derivatives of sucrose

Treatment of sucrose 2,3,3′,4′,6-penta-acetate (1) with methanesulphonyl chloride-N,N-dimethylformamide (reagent A) gave the 1′,4,6′-trichloride 2, the 1′-O-formyl-4,6′-dichloride 3, the 4,6′-dichloride 4, and the 1′,4-di-O-formyl-6′-chloride 5. De-esterification of 3 afforded the unsubstituted 4,6′-dichloride 6 which, on acetylation, gave the corresponding hexa-acetate 7, also prepared by acetylation of 4. In compounds 2, 3, and 4, substitution at C-4 by chloride ion occurred with inversion of configuration. The structure of 5 was confirmed by conversion into the known 6′chloro-6′-deoxysucrose hepta-acetate by de-esterification followed by acetylation. Treatment of sucrose 1′,2,3,3′,4′,6′-hexa-acetate (10) with the reagent gave the 4,6-dichloride 11 and 4-O-formyl-6-chloride 12. The formyl group in 12 was selectively removed by using an anion-exchange resin to give 16. De-esterification of 12 with methanolic sodium methoxide gave 6-chloro-6-deoxysucrose (13) which, on acetylation and benzoylation, afforded the hepta-acetate 14 and the hepta-benzoate 15, respectively. Alternatively, 15 was prepared by the reaction of 1′,2,3,3′,4,4′,6′-hepta-O-benzoylsucrose with reagent A. Treatment of 14 with sodium methoxide in methanol followed by acetylation gave 3,6-anhydrosucrose hexa-acetate (24). Reaction of sucrose 2,3,3′,4,4′-pentabenzoate (17) with reagent A gave the known 1′,6,6′-trichloro-1′,6,6′-trideoxysucrose pentabenzoate (18) and 1′-O-formyl-6,6′-dichloride 19. Treatment of 19 with anion-exchange resins selectively removed the formyl group to give 20. The structure of 20 was confirmed by conversion into the 1′-chlorosulphate-6,6′-dichloride (21). Treatment of sucrose 1′,2,3,3′,4,4′-hexabenzoate (22) with reagent A gave the expected 6,6′-dichloride (23).     

Inhibitory Effects of 1-Deazaadenosine Analogues on HIV Replication and Adenosine Deaminase

Abstract

A series of 2′,3′-dideoxy-N⁶-(cyclo)alkyl-1-deazaadenosine derivatives were synthesized starting from 2,6-dichloro-1-deazapurine (9). The new nucleosides proved to be good inhibitors of HIV-1 replication, the most active being the 2′,3′-dideoxy-2-chloro-N⁶-cycloctyl-1-deazaadenosine (14h, ED₅₀ = 0.4 μ).     

Synthesis and antitumor activity of 1-beta-D-arabinofuranosylcytosine conjugates of cortisol and cortisone.

Superior antitumor activity of 1-β-D-arabinofuranosylcytosine (ara-C) conjugates of prednisolone and prednisone against L1210 leukemic mice, based on ara-C content, has encouraged us to synthesize 5′-(cortisone-21-phosphoryl)-1-β-D-arabinofuranosylcytosine (I) and 5′-(cortisone-21-phosphoryl)-1-β-d-arabinofuranosylcytosine (II) by condensation of N⁴,2′,3′-triacetyl-1-β-d-arabinofuranosylcytosine 5′-monophosphate with cortisol and cortisone in the presence of N,N′-dicyclohexylcarbodiimide at room temperature followed by removing the acetyl groups in 2 N methanolic ammonia in 20% yield. The conjugates I and II inhibited the $\text{in}\text{vitro}$ growth of L1210 by 50% (ED₅₀) at 0.25 μM and 0.07 μM, respectively, while ara-C showed ED₅₀ 0.1 μM. However, the conjugates I and II exhibited 287% and 238% of $\text{T}\text{C}$ at 50 mg/kg/day × 5 doses against L1210 leukemic mice, respectively, while ara-C at 25 mg and 50 mg/kg/day × 5 gave the respective 127% and 110% of $\text{T}\text{C}$.     

Determination of the rotational barriers of atropisomeric polychlorinated biphenyls (PCBs) by a novel stopped-flow multidimensional gas chromatographic technique

The rotational barriers ΔG^‡ (T) of the four atropisomeric polychlorinated biphenyls (PCBs) 2,2′,3,5′,6-pentachlorobiphenyl (PCB 95), 2,2′3,3′,4,6′-hexachlorobiphenyl (PCB 132), 2,2′,3,3′,6,6′-hexachlorobiphenyl (PCB 136), and 2,2′,3,4′,5′,6-hexachlorobiphenyl (PCB 149) were determined via on-line enantiomerization kinetics by a new stopped-flow multidimensional gas chromatographic technique (stopped-flow MDGC) employing Chirasil-Dex as chiral stationary phase for enantiomer separation. The calculated rotational barriers ΔG^‡ (T) of the trichloro-ortho-substituted atropisomers are 184 ± 2 kJ/mol for PCB 95, 189 ± 4 kJ/mol for PCB 132, and 184 ± 1 kJ/mol for PCB 149 at 300°C. The rotational barrier ΔG^‡ (T) of tetrachloro-ortho-substituted PCB 136 is at least (or higher than) 210 kJ/mol at 320°C. Chirality 10:316–320, 1998. © 1998 Wiley-Liss, Inc.     

Fungal bioconversion of toxic polychlorinated biphenyls by white-rot fungus, Phlebia brevispora

Toxic coplanar polychlorinated biphenyls (Co-PCBs) were used as substrates for a degradation experiment with white-rot fungus, Phlebia brevispora TMIC33929, which is capable of degrading polychlorinated dibenzo-p-dioxins. Eleven PCB congener mixtures (7 mono-ortho- and 4 non-ortho-PCBs) were added to the cultures of P. brevispora and monitored by high resolution gas chromatography and mass spectrometry (HRGC/HRMS). Five PCB congeners, 3,3′,4,4′-tetrachlorobiphenyl, 2,3,3′,4,4′-pentachlorobiphenyl, 2,3′,4,4′,5-pentachlorobiphenyl, 3,3′,4,4′,5-pentachlorobiphenyl, and 2,3′,4,4′,5,5′-hexachlorobiphenyl were degraded by P. brevispora. To investigate the fungal metabolism of PCB, each Co-PCB was treated separately by P. brevispora and the metabolites were analyzed by gas chromatography and mass spectrometry (GC/MS) and identified on the basis of the GC/MS comparison with the authentic compound. Meta-methoxylated metabolite was detected from the culture containing each compound. Additionally, para-dechlorinated and -methoxylated metabolite was also detected from the culture with 2,3,3′,4,4′-pentachlorobiphenyl, 2,3′,4,4′,5-pentachlorobiphenyl, and 2,3′,4,4′,5,5′-hexachlorobiphenyl, which are mono-ortho-PCBs. In this paper, we identified the congener specific degradation of coplanar PCBs by P. brevispora, and clearly proved for the first time by identifying the metabolites that the white-rot fungus, P. brevispora, transformed recalcitrant coplanar PCBs.     

Resonance light scattering technique for determination of polychlorinated biphenyls with silver nanoparticles

In this paper, a simple and novel method for the determination of polychlorinated biphenyls (PCBs), using silver nanoparticles (AgNPs) as a resonance light scattering (RLS) probe, is proposed. Under optimized conditions, there existed linear relationships between the enhancing RLS intensity of the system and the concentrations of PCBs in the range 8.0 × 10^?8?1.0 × 10^?6 g mL^?1 for 2,4,4′‐trichlorbiphenyl (PCB28), 9.0 × 10^?8?1.0 × 10^?6 g mL^?1 for 2,2′,5,5′‐tetrachlorbiphenyl (PCB52) and 4.0 × 10^?8?1.0 × 10^?6 g mL^?1 for 3,3′,4,4′‐tetrachlorobiphenyl (PCB77). The corresponding detection limits (S/N = 3) were 2.6 × 10^?8 g mL^?1 for PCB28, 3.3 × 10^?8 g mL^?1 for PCB52 and 6.3 × 10^?9 g mL^?1 for PCB77, respectively. Finally, the mechanism of RLS enhancement was also studied. The results indicated that PCBs were adsorbed on the surface of AgNPs to form larger AgNP–PCB aggregates, resulting in the RLS enhancement of the system. Copyright © 2011 John Wiley & Sons, Ltd.     

Time- and dose-dependent biom arker responses in flounder (Platichthys flesus L.) exposed to benzo[a]pyrene, 2,3,3′,4,4′, 5-hexachlorobiphenyl (PCB-156) and cadmium

Responses in flounder (Platichthys flesus) towards benzo [a]pyrene (BaP), 2,3,3′,4,4′,5-hexachlorobiphenyl (PCB-156), and cadmium (Cd) were investigated in time-course and dose-response studies of selected biomarkers. Measurements of biliary fluorescent BaP metabolites and hepatic concentrations of PCB-156 and cadmium showed that the injected toxicants were rapidly m obilized from the muscle to the liver, but a depot effect was indicated in the highest dose groups of BaP and PCB-156 (12 mg kg^-1 bodyweight). Clearest biomarker responses were found in the induction of hepatic cytochrome P450 1A (CYP1A) enzymes as a response towards BaP and PCB-156 exposure. Maximum induction of CYP1A dependent 7-ethoxyresorufin O-deethylase (EROD) activity was observed after 2 and 8 days in BaP and PCB-156-treated flounder, respectively. Positive dose-effect relationships were observed towards both compounds, but the CYP1A induction was more persistent with PCB exposure than with BaP exposure. In Cd-exposed fish, the hepatic level of metallothionein responded more slowly with highest levels observed after 16 days in the time-study. In the combined BaP + Cd treatment, the CYP1A induction was only slightly suppressed. Aspartate aminotransferase in serum appeared to be responsive towards BaP, but also towards the acetone vehicle in controls in the first part of the exposure period. Hematocrit as well as hepatic activities of aldrin epoxidase, glutathione S-transferase, and UDP-glucuronyl transferase were not responsive to any treatm ent in the present study. In general, the results demonstrate that selected biom arkers in flounder are responsive to PAH, PCB, and heavy metal pollutant exposure, indicating the applicability of this species in future environmental pollution monitoring programmes.     

Polybrominated biphenyls as aryl hydrocarbon hydroxylase inducers: structure-activity correlations

The synthesis of all possible laterally-substituted polybrominated biphenyl (PBB) congeners containing two para bromines is described. Using enzymic, electrophoretic and ligand-binding assays that distinguish between phenobarbitone(PB)- and 3-methylcholanthrene(MC)-type inducers, the synthetic PBBs were evaluated as inducers of liver microsomal drug-metabolizing enzymes in the immature male Wistar rat. 4,4'-Dibromobiphenyl resembled PB in its mode of induction whereas all the meta-brominated derivatives of 4,4'-dibromobiphenyl, namely 3,4,4'-tri, 3,4,4',5-tetra-, 3,3', 4,4'-tetra-, 3,3',4,4',5-penta- and 3,3',4,4',5,5'-hexabromobiphenyl, resembled MC in their mode of induction. The results obtained with 3,4,4'-tribromobiphenyl demonstrate that, in contrast to the polychlorinated biphenyls (PCBs), a single meta halogen substituent is sufficient to abolish the PB-type characteristics of 4,4'-dibromobiphenyl and convert it to a strictly MC-type inducer. PBBs which induce AHH activity must be substituted at both para positions and at one, two, three or four meta positions. Ortho-substitution of PBBs which contain only lateral bromine groups may also give compounds which are aryl hydrocarbon hydroxylase (AHH) inducers. One of the MC-type PBBs, namely 3,3',4,4'-tetrabromobiphenyl, which has been tentatively identified in the commercial PBB mixture, fireMaster BP-6, was at least 50 times more potent as an inducer of AHH activity than the commercial PBB mixture. The induction of AHH by 3,3',4,4'-tetrabromobiphenyl was accompanied by a dose-dependent decrease in both thymus and spleen weights. The thymus and/or spleen weights were decreased in rats treated with the other MC-type PBBs which further supports the correlation between the toxicity of the PBBs and their ability to induce AHH.     

[3H]Dopamine Labeling of D3 Dopaminergic Sites in Human, Rat, and Calf Brain

Abstract: The binding of [³H]dopamine to brain regions of calf, rat, and human was investigated. The calf caudate contained the highest density of [³H]dopamine binding sites, with a B_max value of 185 fmol/mg protein, whereas rat and human striatum contained one-third this number of sites. The K_D values for [³H]dopamine in all tissues were 2–3 nM. Dopaminergic catecholamines (dopamine, apomorphine, 6,7-dihydroxy-2-aminotetralin, and N-propylnorapomorphine) inhibited the binding of [³H]dopamine in all three species, at low concentrations, with IC₅₀ values of 1.5 to 6 nM. Neuroleptics, in contrast, inhibited the binding at high concentrations (with IC₅₀ values of 200 to 40,000 nM). The [³H]dopamine binding sites were saturable, heat-labile, and detectable only in dopamine-rich brain regions; these sites differed from D₂ dopamine sites (labeled by [³H]butyrophenone neuroleptics), and from D_l dopamine sites (labeled by [³H]thioxanthene neuroleptics) associated with the dopamine-stimulated adenylate cyclase. We have, therefore, called these high-affinity [³H]dopamine binding sites D₃ sites. [³H]Apomorphine and [³H]ADTN also appeared to label D₃ sites. These ligands however, were less selective than [³H]dopamine, and labeled sites other than D₃ as well. Assay conditions were important in determining the parameters of [³H]dopamine binding. The optimum conditions for selective labeling of the D₃ dopaminergic sites, using [³H]dopamine, required the presence of EDTA and ascorbate.