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Serotonin, also known as 5-hydroxytryptamine, is an important signaling molecule in the central and peripheral nervous systems of humans. Acting through several receptor types, it helps regulate the normal functioning of the gastrointestinal tract, cardiovascular system and brain. Serotonin signaling has also been implicated in the etiology of several diseases, including depression, anxiety disorders, hypertension and irritable bowel syndrome. The present review focuses on the chemical analysis of serotonin in biological fluids and biomatrices and traces the development and application of early methods based on UV absorbance or fluorescence to more widely used current methods such as high-performance liquid chromatography coupled to mass spectrometry. A brief summary of the biochemistry, metabolism and physiological roles of serotonin is also presented. [ABSTRACT FROM AUTHOR]

Chiral polychlorinated biphenyl (PCB) congeners have been implicated by laboratory and epidemiological studies in PCB developmental neurotoxicity. These congeners are metabolized by cytochrome P450 (P450) enzymes to potentially neurotoxic hydroxylated metabolites (OH-PCBs). The present study explores the enantioselective disposition and toxicity of 2 environmentally relevant, neurotoxic PCB congeners and their OH-PCB metabolites in lactating mice and their offspring following dietary exposure of the dam. Female C57BL/6N mice (8-weeks old) were fed daily, beginning 2 weeks prior to conception and continuing throughout gestation and lactation, with 3.1 μmol/kg bw/d of racemic 2,2',3,5',6-pentachlorobiphenyl (PCB 95) or 2,2',3,3',6,6'-hexachlorobiphenyl (PCB 136) in peanut butter; controls received vehicle (peanut oil) in peanut butter. PCB 95 levels were higher than PCB 136 levels in both dams and pups, consistent with the more rapid metabolism of PCB 136 compared with PCB 95. In pups and dams, both congeners were enriched for the enantiomer eluting second on enantioselective gas chromatography columns. OH-PCB profiles in lactating mice and their offspring were complex and varied according to congener, tissue and age. Developmental exposure to PCB 95 versus PCB 136 differentially affected the expression of P450 enzymes as well as neural plasticity (arc and ppp1r9b) and thyroid hormone-responsive genes (nrgn and mbp). The results suggest that the enantioselective metabolism of PCBs to OH-PCBs may influence neurotoxic outcomes following developmental exposures, a hypothesis that warrants further investigation. [ABSTRACT FROM AUTHOR]

The bile salt export pump (BSEP/Bsep; gene symbol ABCB11/ Abcb11) translocates bile salts across the hepatocyte canalicular membrane into bile in humans and mice. In humans, mutations in the ABCB11 gene cause a severe childhood liver disease known as progressive familial intrahepatic cholestasis type 2. Targeted inactivation of mouse Bsep produces milder persistent cholestasis due to detoxification of bile acids through hydroxylation and alternative transport pathways. The purpose of the present study was to determine whether functional expression of hepatic cytochrome P450 (CYP) and microsomal epoxide hydrolase (mEH) is altered by Bsep inactivation in mice and whether bile acids regulate CYP and mEH expression in Bsep mice. CYP expression was determined by measuring protein levels of Cyp2b, Cyp2c and Cyp3a enzymes and CYP-mediated activities including lithocholic acid hydroxylation, testosterone hydroxylation and alkoxyresorufin O-dealkylation in hepatic microsomes prepared from female and male Bsep mice fed a normal or cholic acid (CA)-enriched diet. The results indicated that hepatic lithocholic acid hydroxylation was catalyzed by Cyp3a/Cyp3a11 enzymes in Bsep mice and that 3-ketocholanoic acid and murideoxycholic acid were major metabolites. CA feeding of Bsep mice increased hepatic Cyp3a11 protein levels and Cyp3a11-mediated testosterone 2β-, 6β-, and 15β-hydroxylation activities, increased Cyp2b10 protein levels and Cyp2b10-mediated benzyloxyresorufin O-debenzylation activity, and elevated Cyp2c29 and mEH protein levels. We propose that bile acids upregulate expression of hepatic Cyp3a11, Cyp2b10, Cyp2c29 and mEH in Bsep mice and that Cyp3a11 and multidrug resistance-1 P-glycoproteins (Mdr1a/1b) are vital components of two distinct pathways utilized by mouse hepatocytes to expel bile acids. [ABSTRACT FROM AUTHOR]

This review examines the monooxygenase, peroxidase, and peroxygenase properties of cytochrome P450 (P450)1 enzymes and their mechanisms of action in archaeal, bacterial, and mammalian systems. In the P450 catalytic cycle, a transient iron oxo monooxygenating species is generated that reacts with substrate to produce a monooxygenated product. We describe results of early investigations that endeavored to trap and detect this elusive monooxygenating species, as well as results of experiments that attempted to generate and characterize this active oxidant spectroscopically after reacting ferric P450 enzymes with peroxy compounds (e.g. peroxides, peracids) or single oxygen atom donors (e.g. periodate, iodosobenzene). Surrogate oxidants were able to promote P450-catalyzed monooxygenations in a manner similar to that of O2/NAD(P)H, suggesting involvement of a common transitory monooxygenating species in the two pathways. This common P450 oxidant was characterized as a porphyrin radical iron(IV) oxo complex and assigned a Compound I structure (Por+FeIV=O) exhibiting a formal Fe(V) oxidation state. Other reactive oxidants, such as the ferric oxenoid complex (PorFeIII=O), ferryloxy radical species (PorFeIV–O), and perferryloxo entity (PorFeV=O), were also proposed to function as P450 monooxygenating species. We also discuss the possible involvement of the ferriperoxo (PorFeIII–OO−) and ferrihydroperoxo (PorFeIII–OOH) species as alternative oxidants in P450-mediated monooxygenation reactions. [ABSTRACT FROM AUTHOR]

Abstract: In the present study, we examined the expression of CYP2S1 mRNA and protein in tissues from male and female rats and investigated aryl hydrocarbon receptor (AhR)-mediated regulation. CYP2S1 mRNA was detected by RT-PCR in all rat tissues examined, except for the adrenal gland, and no sex-dependent differences were observed. To study the regulation of CYP2S1 mRNA expression by AhR agonists, rats were treated with 3-methylcholanthrene (3-MC; 25mg/kg/day×3 days) or with a single intraperitoneal injection of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) at various dosages (0, 1, 5, 10, 50, 100μg/kg). CYP2S1 mRNA levels were increased in lung, stomach, jejunum and ileum following treatment with 3-MC and in lung, liver and kidney tissues following treatment with TCDD. Induction of CYP2S1 mRNA was greater with TCDD than 3-MC treatment and was more pronounced in lung than other tissues. Antiserum raised against a peptide corresponding to the C-terminus of CYP2S1 was used to measure relative CYP2S1 protein expression by immunoblot analysis. An immunoreactive CYP2S1 protein band with an approximate molecular weight of 50kDa was detected in microsomes of rat lung, stomach and kidney, but not other tissues. Unlike CYP2S1 mRNA, CYP2S1 protein levels were not increased after treatment with 3-MC or the highest dosage of TCDD, indicating that CYP2S1 protein expression was less sensitive than mRNA expression to AhR-mediated regulation. Our study is the first to characterize CYP2S1 mRNA and protein expression in rats, and from the results obtained, we conclude that AhR is involved in the transcriptional regulation of CYP2S1 in rats. [Copyright &y& Elsevier]

This study investigated the spectral interactions of hepatic microsomal cytochrome P450 (CYP) enzymes with four symmetrical polychlorinated biphenyls (PCBs): 2,2′,4,4′-tetrachlorobiphenyl (PCB 47); 2,2′,5,5′-tetrachlorobiphenyl (PCB 52); 2,2′,6,6′-tetrachlorobiphenyl (PCB 54); and 3,3′,4,4′-tetrachlorobiphenyl (PCB 77). The PCBs were selected to explore structure–activity relationships and the effect of the chlorination pattern on PCB–CYP spectral interactions. To examine CYP enzyme specificity, difference spectra were measured with hepatic microsomes prepared from control, phenobarbital (PB)-, 3-methylcholanthrene (MC)-, and dexamethasone (DEX)-treated rats in the absence and presence of CYP-specific antibodies. The four PCB congeners elicited a type I spectral change with all hepatic microsomal preparations. The binding efficiency of the PCBs was highest with microsomes from PB-treated rats. The largest absorbance change and highest binding efficiency were observed with PCB 54, the most non-coplanar congener tested. Antibody inhibition and CYP immunoquantitation data showed that the PCBs bind to CYP1A, CYP2B, CYP2C and CYP3A enzymes to varying degrees. For example, PCB 47, 52, and 54 bind preferentially to CYP2B and to a lesser extent to CYP3A enzymes in microsomes from PB-treated male rats; PCB 52 binds primarily to CYP3A enzymes in microsomes from DEX-treated female rats; and PCB 54 binds to CYP3A and to CYP2C enzymes in microsomes from control male rats. The study demonstrated that the extent of PCB–CYP binding interaction was dependent on the chlorination pattern of the PCB and on the relative abundance of individual CYP enzymes in hepatic microsomes. [Copyright &y& Elsevier]

An investigation involving raccoons as a sentinel species at the Paducah Gaseous Diffusion Plant (PGDP) and Ballard Wildlife Management Area in western Kentucky (USA) delineated the extent of exposure to polychlorinated biphenyls (PCBs). Three separate measures of hepatic cytochrome P450 (CYP) induction were used to evaluate raccoon physiological responses to PCB exposure. Hepatic CYP induction was estimated via determination of total CYP, dealkylase activities, and immunoreactive proteins. There were no differences in raccoon biomarker responses between study sites. Significant relationships between and among PCB residues and biomarkers indicated that hepatic CYP induction had occurred in response to PCB exposure. Pentoxyresorufin O-deethylase (PROD) activity, CYP1A1, and CYP1A2 were biomarkers most closely associated with PCB exposure. The rank order of responses was CYP1A1 > CYP1A2 > PROD > ethoxyresorufin O-deethylase (EROD) as related to raccoon liver PCB concentrations, whereas the order was CYP1A1 > PROD > EROD > CYP1A2 when regressed with total PCB concentrations in abdominal fat. [ABSTRACT FROM AUTHOR]

The influence of exogenous growth hormone (GH) on pubertal maturation, as assessed by growth, age of preputial separation, testicular development, and hepatic expression of sexually dimorphic cytochrome P450 (CYP) enzymes, was investigated. Treatment of 22-day old prepubertal intact male rats with twice daily subcutaneous (sc) injections of rat recombinant GH (0.12 µg/g body weight) for 12 or 21 days did not affect body weight, skeletal growth, or testicular weight. By comparison, GH suppressed hepatic CYP2C11 enzyme activity, protein, and mRNA levels but induced CYP2C12 expression. GH suppressed CYP2C11 expression by approximately 60% in prepubertal rats as compared with 30% in adult rats, whereas it increased CYP2C12 levels to 80% of the normal female levels but had no effect in adult male rats. Twice daily intravenous injections of GH suppressed CYP2C11 only. Increasing the sc dose of GH 30-fold produced little or no additional change in CYP2C11 or CYP2C12 expression, whereas it modestly increased body weight and skeletal growth and reduced testicular weight. Overall, the present study provides the first demonstration that prepubertal administration (22-33 days of age) of GH at a pharmacologically relevant dose (0.12 µg/g twice daily) suppressed hepatic expression of CYP2C11 in 34-day-old intact male rats, suggesting that in this age group the liver is intrinsically responsive to transcription factors involved in the regulation of GH-dependent, sex-specific CYP gene expression. A higher dose (3.6 µg/g) of GH administered during the prepubertal period was required to elicit a modest effect on somatic growth and gonadal development.Key words: cytochrome P450, CYP2C11, CYP2C12, growth hormone, preputial separation, pubertal development, testosterone.On a examiné l'effet de l'hormone de croissance (GH) exogène sur la maturation pubertaire, tel que déterminé par la croissance, l'âge du décollement préputial, le développement testiculaire et l'expression hépatique d'enzymes sexuellement dimorphiques du cytochrome P450 (CYP). Le traitement de rats mâles intacts prépubertaires de 22 jours au moyen d'injections sous-cutané (sc) biquotidiennes de GH recombinante de rat (0,12 µg/g poids corporel), pendant 12 ou 21 jours, n'a pas eu d'effet sur le poids corporel, la croissance du squelette ou le poids testiculaire. Par comparaison, la GH a supprimé les taux d'ARNm, de protéines et l'activité enzymatique de CYP2C11 et induit l'expression de CYP2C12 dans le foie. La GH a supprimé l'expression de CYP2C11 d'approximativement 60 % chez les rats prépubertaires comparativement à 30 % chez les rats adultes, alors qu'elle a augmenté les taux de CYP2C12 à 80 % des taux normaux des rats femelles, sans toutefois avoir d'effet sur les rats mâles adultes. Les injections intraveineuse (iv) biquotidiennes de GH n'ont supprimé que CYP2C11. L'augmentation de la dose sc de GH d'un facteur 30 a provoqué peu ou pas de variation additionnelle de l'expression de CYP2C11 ou de CYP2C12, tandis qu'elle a augmenté légèrement le poids corporel et la croissance du squelette, et réduit le poids testiculaire. Cette étude est la première à démontrer que l'administration prépubertaire (âge de 22 à 33 jours) de GH à une dose pharmacologiquement appropriée (0,12 µg/g deux fois par jour) a supprimé l'expression hépatique de CYP2C11 chez des rats mâles intacts de 34 jours. Ces résultats permettent de croire que, chez les animaux de ce groupe d'âge, le foie est intrinsèquement sensible aux facteurs de transcription mis en cause dans la régulation, selon le sexe, de l'expression GH dépendante des gènes CYP. L'administration d'une plus forte dose de GH (3,6 µg/g) durant la période prépubertaire a été nécessaire pour provoquer un léger effet sur la croissance somatique et le développement gonadique.Mots clés : cytochrome P450, CYP2C11, CYP2C12, hormone de croissance, décollement préputial, développement pubertaire, testostérone.[Traduit par la Rédaction] [ABSTRACT FROM AUTHOR]

In the present study, we investigated the oxidative biotransformation of 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47) and 2,2′,4,4′,5-pentabromodiphenyl ether (BDE-99) by liver microsomes from wild lesser snow geese ( Chen caerulescens caerulescens ) and domesticated Japanese quail ( Coturnix japonica ). Formation of hydroxy-metabolites was analyzed using an ultra-high performance liquid chromatography-tandem mass spectrometry-based method. Incubation of BDE-47 with avian liver microsomes produced sixteen hydroxy-metabolites, eight of which were identified using authentic standards. The major metabolites formed by liver microsomes from individual lesser snow geese were 4-hydroxy-2,2′,3,4′-tetrabromodiphenyl ether (4-OH-BDE-42), 3-hydroxy-2,2′,4,4′-tetrabromodiphenyl ether (3-OH-BDE-47), and 4′-hydroxy-2,2′,4,5′-tetrabromodiphenyl ether (4′-OH-BDE-49). By comparison, 4-OH-BDE-42 and 4′-OH-BDE-49, but not 3-OH-BDE-47, were major metabolites of Japanese quail liver microsomes. Unidentified metabolites included monohydroxy- and dihydroxy-tetrabromodiphenyl ethers. Incubation of BDE-99 with avian liver microsomes produced seventeen hydroxy-metabolites, twelve of which were identified using authentic standards. The major metabolites formed by lesser snow goose liver microsomes were 2,4,5-tribromophenol, 3-OH-BDE-47, 4′-OH-BDE-49, 4-hydroxy-2,2′,3,4′,5-pentabromodiphenyl ether (4-OH-BDE-90), and 5′-hydroxy-2,2′,4,4′,5-pentabromodiphenyl ether (5′-OH-BDE-99). By comparison, the major metabolites produced by liver microsomes from Japanese quail included 6-hydroxy-2,2′,4,4′-tetrabromodiphenyl ether (6-OH-BDE-47) and 2-hydroxy-2′,3,4,4′,5-pentabromodiphenyl ether (2-OH-BDE-123), but not 3-OH-BDE-47. Unidentified metabolites consisted of monohydroxy-pentabromodiphenyl ethers, monohydroxy-tetrabromodiphenyl ethers and dihydroxy-tetrabromodiphenyl ethers. Another difference between the two species was that formation rates of BDE-47 and BDE-99 metabolites were greater with liver microsomes from male than female Japanese quail, but a sex difference was not observed with lesser snow geese. [ABSTRACT FROM AUTHOR]

Cytochrome P450 (CYP) enzymes are important for the metabolism of many drugs. While there is information on their identity and ontogeny in humans and rodents, similar data in sheep are lacking. In the present study, cDNA sequences of several CYP enzymes (CYP2A6, CYP2C19, CYP2D6) were cloned by rapid amplification of cDNA ends. In adult, newborn and fetal sheep the mRNA and protein levels of these CYPs and the regulatory factor, hepatic nuclear factor 4ɑ (HNF4ɑ) were determined in liver samples using real-time PCR and western blotting. The effect of antenatal glucocorticoid on these enzymes was also studied by i.v. infusion of cortisol (0.45 mg h[–1]; 80 h) to another group of fetuses. The mRNA and protein levels of the CYPs and HNF4ɑ were low or absent in the fetus, followed by increasing levels in the newborn and adult. Fetal cortisol administration significantly increased the mRNA and protein levels of CYP2D6. Moreover, the correlation observed between the CYP and HNF4ɑ mRNA levels suggests a possible regulatory role for this transcription factor. The findings suggest that fetal and newborn lambs have a low ability to metabolise drugs that are substrates of these enzymes, and that this ability increases with advancing postnatal age, similar to the situation in humans. Cytochrome P450 (CYP) enzymes are important for drug metabolism, but there is limited information on their development in the fetus and newborn. Their levels in sheep liver were low in the fetus, increased after birth and fetal administration of cortisol increased their levels, particularly of CYP2D6. We conclude that drug metabolism in the fetus is limited by the low CYP expression and that the prepartum fetal cortisol rise may stimulate their expression. [ABSTRACT FROM AUTHOR]

Polar bears are at the top of the Arctic marine food chain and are subject to exposure and bioaccumulation of environmental chemicals of concern such as polybrominated diphenyl ethers (PBDEs), which were widely used as flame retardants. The aim of the present study was to evaluate the in vitro oxidative metabolism of 2,2′,4,4′-tetrabrominated diphenyl ether (BDE-47) and 2,2′,4,4′,5-pentabrominated diphenyl ether (BDE-99) by polar bear liver microsomes. The identification and quantification of the hydroxy-brominated diphenyl ethers formed were assessed using an ultra-high performance liquid chromatography-tandem mass spectrometry-based method. Incubation of BDE-47 with archived individual liver microsomes, prepared from fifteen polar bears from northern Canada, produced a total of eleven hydroxylated metabolites, eight of which were identified using authentic standards. The major metabolites were 4′-hydroxy-2,2′,4,5′-tetrabromodiphenyl ether and 5′-hydroxy-2,2′,4,4′-tetrabromodiphenyl ether. Incubation of BDE-99 with polar bear liver microsomes produced a total of eleven hydroxylated metabolites, seven of which were identified using authentic standards. The major metabolites were 2,4,5-tribromophenol and 4-hydroxy-2,2′,3,4′,5-pentabromodiphenyl ether. Among the CYP specific antibodies tested, anti-rat CYP2B was found to be the most active in inhibiting the formation of hydroxylated metabolites of both BDE-47 and BDE-99, indicating that CYP2B was the major CYP enzyme involved in the oxidative biotransformation of these two congeners. Our study shows that polar bears are capable of forming multiple hydroxylated metabolites of BDE-47 and BDE-99 in vitro and demonstrates the role of CYP2B in the biotransformation and possibly in the toxicity of BDE-47 and BDE-99 in polar bears. [ABSTRACT FROM AUTHOR]

Abstract: UDP glucuronosyltransferases (UGTs) are important for the metabolism of many drugs. To understand the ontogeny of these enzymes in sheep (Ovis aries), knowledge of their expression levels at different developmental stages is important. cDNA sequences of six UGTs (UGT1A1, UGT1A3, UGT1A4, UGT1A6 and UGT1A9) were cloned in sheep liver by rapid amplification of cDNA ends. The mRNA and protein levels of the enzymes in sheep liver (adult n=4; newborn n=3; fetus n=3) were determined using PCR and Western blots. mRNA levels in adult were very high followed by newborn and then fetus. However, no protein bands were detected on the Western blots of sheep hepatic microsomal proteins using several different antibodies against human UGTs. The effect of antenatal glucocorticoid administration was also studied by infusion of cortisol (0.45mg/h; 80h) to another group of fetuses (n=5). This did not result in any significant changes in fetal mRNA levels. However, the correlation observed between the UGT enzymes and hepatocyte nuclear factor 4α (HNF4α) suggests a possible regulatory role for this transcription factor in sheep. We postulate that fetal and newborn lambs may have a reduced ability to metabolize drugs that are substrates of these enzymes. [Copyright &y& Elsevier]

Abstract: Polychlorinated biphenyls (PCBs) elicit a spectrum of biochemical and toxic effects in exposed animals. In the present study, we assessed the effect of PCB structure, using four symmetrically-substituted PCBs, on cytochrome P450 (CYP)-mediated methoxy-, ethoxy- and benzyloxyresorufin O-dealkylase (MROD, EROD and BROD, respectively) activities. We found that 2,2′,4,4′-tetrachlorobiphenyl (PCB 47), 2,2′,5,5′-tetrachlorobiphenyl (PCB 52), 2,2′,6,6′-tetrachlorobiphenyl (PCB 54) and 3,3′,4,4′-tetrachlorobiphenyl (PCB 77) inhibited alkoxyresorufin O-dealkylase activities in hepatic microsomes from 3-methylcholanthrene (MC) or phenobarbital (PB)-treated rats. Measurement of the in vitro inhibitory potencies of the tetrachlorobiphenyls revealed that MROD, EROD and BROD activities were differentially inhibited and the degree of inhibition was determined by the chlorination pattern of the PCB. PCB 77 was more potent than PCB 47 or PCB 52 at inhibiting MROD and EROD activities in hepatic microsomes from MC-treated rats, while no inhibition of either activity was observed with PCB 54. In contrast, BROD activity measured in hepatic microsomes from PB-treated rats was inhibited by PCB 47, PCB 52 and PCB 54 but not by PCB 77. The mode of inhibition for each activity was also evaluated statistically. Inhibition of the alkoxyresorufin O-dealkylase activities could not be discerned in hepatic microsomes from corn oil-treated rats because the activities were inherently too low. No evidence for mechanism-based inhibition of MROD, EROD or BROD activities or an effect via CYP reductase was found. The results demonstrate that relatively coplanar PCBs such as PCB 77 preferentially inhibit EROD and MROD activities, whereas noncoplanar PCBs such as PCB 54 preferentially inhibit BROD activity. [Copyright &y& Elsevier]

Cytochrome P4501A (CYP1A) and the 70-kDa stress protein (HSP70) were determined using Western blotting in the ovary and liver of juvenile female rainbow trout (Oncorhynchus mykiss) exposed for 4 days to β-naphthoflavone (βNF) following a single intraperitoneal injection. Ovarian CYP1A protein was observed in both control and βNF-exposed fish, indicating constitutive and inducible expression of CYP1A in immature trout ovaries. CYP1A protein levels determined using densitometry were 14- and 46-fold greater in βNF-exposed trout compared to controls in the liver and ovary, respectively. Hepatic microsomal ethoxyresorufin O-deethylase (EROD) activity, a specific catalytic marker of CYP1A, was also induced 38-fold above controls following βNF exposure. Hepatic HSP70 protein expression was significantly higher in whole cell homogenates, but not in cytosolic fractions, collected from βNF-exposed fish in comparison to control fish. There was no difference in ovarian HSP70 levels determined in whole cell homogenates between control and βNF-exposed fish. The observation that unlike liver, ovarian HSP70 expression remained unchanged following induction of CYP1A protein may be related to the sensitivity of the teleost ovary to environmental toxicants that act as aryl hydrocarbon receptor agonists. [Copyright &y& Elsevier]

In this study, the levels of polybrominated diphenyl ethers (PBDEs), HO-PBDEs, and bromophenols were monitored in starling chick plasma samples collected in Delta (British Columbia, Canada) close to the Vancouver municipal landfill and in Glen Valley, a rural area in British Columbia. The in vitro formation of hydroxylated metabolites of 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47) and 2,2′,4,4′,5-pentabromodiphenyl ether (BDE-99) was also investigated using starling chick liver microsomes. Total PBDE plasma levels were approximately 60 times higher in starling chicks from Delta than from Glen Valley, suggesting that the Delta site is a major source of PBDEs for the local population of starlings and that PBDEs previously measured in starling eggs are bioavailable to chicks. In both locations, BDE-47 and BDE-99 were the two major congeners present at similar concentrations, suggesting contamination with the Penta-BDE mixture. Among the several possible hydroxylated metabolites of PBDEs monitored in starling plasma, only 2,4,5-tribromophenol was detected and its levels did not exceed 18 ± 7 pg/mL. Also, several hydroxylated metabolites of BDE-47 and BDE-99 were formed by starling chick liver microsomes, but in low amounts. Therefore, our data consistently suggest that oxidative metabolism of PBDEs in starling chicks proceeds at low rate in vivo and in vitro . In conclusion, the landfill located in Delta is a relevant source of bioavailable PBDEs for the local starling population. Because of the limited ability of starling chicks to metabolize PBDEs, these compounds are likely to bioaccumulate in starlings over time. The possible toxicological implications of PBDEs bioaccumulation in starlings are currently unknown and require further research. [ABSTRACT FROM AUTHOR]

Abstract: We previously reported in vivo induction of cytochrome P450 1A (CYP1A) by β-naphthoflavone in skin and liver biopsies of captive harbour seals (Phoca vitulina richardsi). The present study evaluated CYP1A expression (immunoblot analysis and ethoxyresorufin O-deethylase activity-EROD) in harbour seals using two study designs: i) skin and liver biopsies from 20 harbour seal pups captured from coastal British Columbia (BC, Canada) and temporarily housed in captivity; and ii) skin biopsies from 42 free-ranging harbour seals captured and sampled on-site in multiple locations in BC and Washington State (USA). Toxic Equivalency Quotients (TEQs) were calculated for polychlorinated biphenyl, polychlorinated dibenzo-p-dioxin, and polychlorinated dibenzofuran residues measured in blubber from a subset of study animals (n =30). CYP1A data from the seal pups held temporarily in captivity show that CYP1A protein levels were greater in liver than skin and that CYP1A protein and EROD activity were correlated in skin and liver. However, analysis of free-ranging seals from different sites revealed that blubber organochlorine TEQ values did not correlate with skin CYP1A levels. CYP1A protein levels and EROD activities in skin of seal pups from the BC locations and from Puget Sound were relatively low, possibly reflecting contaminant levels that were not high enough to elicit a response, a small sample size, or methodological limitations. Our results show that CYP1A measurements in skin show promise as a biomarker of contaminant exposure, but that refinements to techniques and a larger sample size are needed. [Copyright &y& Elsevier]