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1.
Benzo(a)pyrene (BaP) and polychlorinated biphenyls (PCBs) often co-exist in contaminated environments. Polychlorobiphenylols (OH-PCBs), formed by CYP-dependent monooxygenation of PCBs, are potent inhibitors of the glucuronidation of hydroxylated BaP metabolites. We hypothesized that OH-PCBs could drive the biotransformation of (-)BaP-7,8-dihydrodiol (BaP-7, 8-D) away from detoxication and towards formation of the reactive metabolite. A mixture of five OH-PCBs with 4-6 Cl atoms was infused into isolated, perfused, biliary intact livers (n=3 fish) removed from 3-methylcholanthrene-induced channel catfish. Controls (n=3) were infused with vehicle. Subsequently, [3H]-BaP-7, 8-D was infused into each liver and bile was collected for 1 h. The livers were taken for analysis of metabolites and DNA adducts. Induction status was confirmed by EROD assay. Bile was analyzed for metabolites. It was found that preinfusion of the mixture of OH-PCBs reduced the extent of glucuronidation of BaP-7, 8-D and increased the formation of DNA adducts 5-fold over controls. GSH conjugates, tetrols and triols were increased in the OH-PCB-infused fish, providing further support for our hypothesis that if the glucuronidation were inhibited, CYP-dependent activation would increase. These studies suggest a mechanism for synergy of toxicity of PAH and PCBs.  相似文献   

2.
Juvenile turbot (Scophthalmus maximus) were injected intraperitoneally with either corn oil or 5 mg/kg benzo[a]pyrene (BaP) dissolved in corn oil and sampled I and 3 days after injection. After 1 day, no elevation of 7-ethoxyresorufin O-deethylase (EROD) activity was observed, however bile metabolites (BaP-7,8 dihydrodiol representing 70% of the total metabolites) and a single hepatic DNA adduct spot (0.47 adducts/10(8) nucleotides) identified by 32P-postlabelling were formed. No BaP metabolites or DNA adducts were observed in either control or carrier control fish. Fish sampled after 3 days reported 5-fold higher (P < 0.05) levels of EROD activity, a shift in the bile metabolite profile towards BaP phenol formation (1OH and 30H BaP comprising up to 60% of total metabolites detected) and the formation of two adduct spots (0.86 and 0.71 adducts/10(8) nucleotides). These results show that BaP can be metabolised and form hydrophobic DNA adducts in turbot without EROD elevation. Following EROD elevation, a shift in the profile of both BaP metabolites and BaP metabolite-DNA interactions occurs indicative of other oxidative processes.  相似文献   

3.
Bioaccumulation of endocrine disruptors in marine mammals positioned at the top of the food chain is of toxicological concern. Livers from four pups and ten adult harbor seals (Phoca vitulina) stranded in San Francisco Bay (SFB) and the Gulf of Maine (GOM) were analyzed for polychlorinated biphenyls (PCBs) and their hydroxylated metabolites (OH-PCBs). We used GC–ECD and GC–NCI/MS to investigate the presence of 28 PCBs and 8 OH-PCB metabolites, respectively. Σ28PCB concentrations (di- to octa-CBs) ranged from 1.81 to 35.9 μg/g lipid with a median of 6.53 for the seal pups and 2.31 to 249 μg/g lipid with a median of 28.9 for the adult seals. Σ8OH-PCB concentrations (penta- to hepta-OH-PCBs) ranged from 0.02 to 0.69 μg/g lipid with a median of 0.04 for the adult seals, i.e., at much lower concentrations than those for PCBs. Ratios of OH-PCBs to PCBs (0.24% on average) were comparable to those in beluga whale, but were lower than ratios in human livers. The OH-PCB profiles were slightly different between SFB and GOM seal livers, although similar PCB congener patterns were observed. Generally, 4-OH-CB107 was found predominantly in seal livers and was the only OH-PCB detectable in most of seal pup livers. This study provides information on OH-PCBs in seals, adding to the scarce exposure data for these chemicals.  相似文献   

4.
Polar bears bioaccumulate lipophilic pollutants, including polychlorinated biphenyls (PCBs), into their bodies from their exclusive diet of marine organisms. Hydroxylated PCB metabolites (OH-PCBs) have been found in plasma, presumably due to CYP-dependent biotransformation of PCBs in liver. Little is known about the phase 2 metabolism of hydroxylated xenobiotics in polar bears. The objective of this study was to examine UDP-glucuronosyltransferase (UGT) activity with OH-PCBs and a hydroxylated polycyclic aromatic hydrocarbon, 3-hydroxy-benzo(a)pyrene (3-OH-BaP), in polar bear liver. Samples of frozen polar bear liver were used to prepare microsomes. UGT activity with 3-OH-BaP in Brij-treated microsomes, measured by a fluorescence assay, was readily measurable with protein concentrations in assay tubes of up to 10 μg/ml, but dropped off very sharply at higher protein concentrations. The apparent Km for 3-OH-BaP was 1.71 ± 0.04 μM, and Vmax 1.26 ± 0.16 nmol/min/mg protein (mean ± SD, n=3). UGT activities with a model tetrachloro-OH-PCB (4′-OH-CB72) and a model hexachloro-OH-PCB (4′-OH-CB159) were assayed with [14-C]-UDPGA and separation of the [14-C]-glucuronide by ion-pair extraction and thin-layer chromatography. [14-C]-glucuronide conjugates were readily formed by polar bear liver microsomes in the absence of added substrate, apparently from contaminants present in liver. This phenomenon was not observed using hepatic microsomes from laboratory-held catfish. Glucuronidation efficiency was much higher with 4′-OH-CB72 (Km 7.3 μM; Vmax 1.55 nmol/min/mg) than 4′-OH-CB159 (Km 16.1 μM; Vmax 0.46 nmol/min/mg). The identities of the aglycones present in polar bear liver are not known, but could include OH-PCBs or hydroxylated metabolites of other persistent organic pollutants. This study demonstrates that UGT with high activity for 3-OH-BaP and other substrates is present in polar bear liver.  相似文献   

5.
Turbot (Scophthalmus maximus) and mussel (Mytilus edulis) microsomes were incubated with DNA to examine if microsomal in vitro metabolism of BaP could result in DNA adducts detected by 32P-postlabelling. Turbot DNA was incubated with benzo[a]pyrene (BaP), NADPH and microsomal activating systems prepared from either livers of unexposed turbot, turbot exposed to BaP or β-naphthoflavone (ß-NF) or digestive glands from mussels. The β-NF activating system generated the highest levels of DNA adducts detected in this study (451.7 adducts per 108 nucleotides) and were distributed in three discrete adduct TLC spots, one of which (97% of the total adducts) co-migrated with the 32P-postlabelled BaP 7,8-diol, 9,10-epoxide-N2-guanine adduct. Fewer adducts (P <0.05) were generated by BaP-induced microsomes (9.4–30.6 adducts per 108 nucleotides) but levels were higher (P <0.05) than those generated from untreated fish (3.5 adducts per 108 nucleotides). Co-incubation with 500 μM α-naphthoflavone (α-NF) resulted in 97–99% inhibition in adduct formation implicating cytochrome P450-dependent (CYP) bioactivation however there was some evidence for carry over of BaP in the liver microsomal preparations from BaP injected fish. In contrast to the fish activating systems, no DNA adducts were observed when mussel microsomes were incubated with BaP, DNA and NADPH.  相似文献   

6.
Sediments and organisms were examined for concentrations of organic and metal contaminants from near the Los Angeles County (JWPCP) municipal outfall at Palos Verdes (PV) station 7-3, the Los Angeles City (Hyperion) municipal outfall at Santa Monica Bay (SMB) station 6-4 and reference station SMB 2–3 near Malibu Beach. Flows and mass emission rates of suspended solids, PCBs, Cd and Zn were similar at the two outfalls. Mass emission rate of copper was almost twice as high from Hyperion as from JWPCP, while mass emission rate of DDTs was an order or magnitude higher from JWPCP than from Hyperion.Surficial sediments at PV 7-3 were enriched in most contaminants relative to SMB 6-4 and relative to the mass emission rates of contaminants from the JGVPCP and Hyperion outfalls. Some of this enrichment could be accounted for by the greater accumulation of organic material, measured as total volatile solids, at PV 7-3 relative to SMB 6-4. Some might be accounted for by resurfacing of more contaminated historical deposits buried at PV 7-3. Some of the enrichment of DDTs relative to PCBs could be accounted for by the greater abundance of oxygenated metabolites of PCBs (PCBols) relative to DDTs (DDTols) in sediments.The degree of contamination of organisms by DDTs increased with proximity to PV 7-3 but contamination by PCBs was similar at PV 7-3 and SMB 6-4. DDT concentrations in fish livers ranged from 12 ± 4 ( ) mg/wet kg in longspine combfish from SMB 2–3 to 610 ± 105 (n = 5) mg/wet kg in Pacific sanddab from PV 7-3. DDT concentrations in fish gonads ranged from 0·003 ± 0·003 (n = 5) mg/wet kg in yellowchin sculpin from SMB 6-4 to 1.5 ± 6 (n = 3) mg/wet kg in Pacific sanddabs from PV 7-3. PCB concentrations in fish livers ranged from 1·2 ± 0·4 (n = 4) mg/wet kg in yellowchin sculpin from SMB 2–3 to 16 ± 3 (n = 6) in Pacific Sanddab from SMB 6-4. DDT and PCB concentrations in invertebrate hepatopancreas were only slightly lower than those in fish livers. DDTols and PCBoIs comprised an average of 91 % of the total of parent compounds and oxygenated metabolites in sediments and 66 % in livers and hepatopancreas. Trace metals were frequently decreased in livers and hepatopancreas from near outfalls even though they were highly elevated in sediments.Comparison of sediment and tissue chlorinated hydrocarbon data with that from Elliot and Commencement Bays, Puget Sound, indicated that none of the southern California coastal stations considered in this study were sufficiently lacking contamination to be considered as adequate control sites.  相似文献   

7.
Intestinal metabolism plays a significant role in the bioavailability of ingested environmental toxicants. In this study, the potential for first pass, phase 2 biotransformation of benzo[a]pyrene-7,8-dihydrodiol (BaP-7,8-diol) in intestinal mucosa was examined. Sulfotransferase and Uridine 5'-Diphospho-Glucuronyl-transferase activity were measured in cytosol, and microsomes respectively. Radiolabeled conjugation products were analyzed by TLC and high-performance liquid chromatography (HPLC). The results indicated that BaP-7,8-diol was a poor substrate for intestinal sulfotransferase. Vmax for the sulfation of BaP-7,8-diol was 0.002 nmol mg-1 min-1, which is at least three orders of magnitudes lower than the Vmax for phenolic BaP metabolites. Studies with 3'phosphoadenosine-5' phosphosulfate (PAP)-35S as co-substrate showed that an unidentified compound in the reaction mixture was sulfated, dependent on the BaP-7,8-diol concentration. This could indicate that BaP-7,8-diol was interacting with a regulatory site on the enzyme and stimulated sulfation of an endogenous molecule in cytosol. Kinetic analysis of microsomal glucuronidation resulted in a Vmax of 0.30 nmol mg-1 min-1 (+/- 0.06 S.D., n = 4), with a Km of 23.39 microM (+/- 2.66 S.D.). The Km for the co-substrate UDP-glucuronic acid was approximately 43 microM. The slow rates for sulfation and glucuronidation of BaP-7,8-diol may explain its relatively high systemic availability when ingested or produced by intestinal phase 1 enzymes.  相似文献   

8.
Polar bears bioaccumulate lipophilic pollutants, including polychlorinated biphenyls (PCBs), into their bodies from their exclusive diet of marine organisms. Hydroxylated PCB metabolites (OH-PCBs) have been found in plasma, presumably due to CYP-dependent biotransformation of PCBs in liver. Little is known about the phase 2 metabolism of hydroxylated xenobiotics in polar bears. The objective of this study was to examine UDP-glucuronosyltransferase (UGT) activity with OH-PCBs and a hydroxylated polycyclic aromatic hydrocarbon, 3-hydroxy-benzo(a)pyrene (3-OH-BaP), in polar bear liver. Samples of frozen polar bear liver were used to prepare microsomes. UGT activity with 3-OH-BaP in Brij-treated microsomes, measured by a fluorescence assay, was readily measurable with protein concentrations in assay tubes of up to 10 g/ml, but dropped off very sharply at higher protein concentrations. The apparent Km for 3-OH-BaP was 1.71 +/- 0.04 microM, and Vmax 1.26 +/- 0.16 nmol/min/mg protein (mean +/- SD, n=3). UGT activities with a model tetrachloro-OH-PCB (4'-OH-CB72) and a model hexachloro-OH-PCB (4'-OH-CB159) were assayed with [14-C]-UDPGA and separation of the [14-C]-glucuronide by ion-pair extraction and thin-layer chromatography. [14-C]-glucuronide conjugates were readily formed by polar bear liver microsomes in the absence of added substrate, apparently from contaminants present in liver. This phenomenon was not observed using hepatic microsomes from laboratory-held catfish. Glucuronidation efficiency was much higher with 4'-OH-CB72 (Km 7.3 microM; Vmax 1.55 nmol/min/mg) than 4'-OH-CB159 (Km 16.1 microM; Vmax 0.46 nmol/min/mg). The identities of the aglycones present in polar bear liver are not known, but could include OH-PCBs or hydroxylated metabolites of other persistent organic pollutants. This study demonstrates that UGT with high activity for 3-OH-BaP and other substrates is present in polar bear liver.  相似文献   

9.
Freshly prepared homogenates were used to assess the relative ability of winter flounder (Pseudopleuronectes americanus) liver and intestinal mucosal cells to metabolize the polycyclic aromatic hydrocarbon (PAH) benzo[a]pyrene (BaP) and its proximate carcinogenic metabolite, BaP-7,8-dihydrodiol (7,8-Diol). Data obtained from homogenates prepared from fish previously fed β-naphthoflavone (BNF) indicated that both tissues had similar abilities to metabolize either BaP or 7,8-Diol on a per gram of protein basis. Metabolite profiles produced indicate that water-soluble metabolite formation is favored at low doses. These findings support the hypothesis that the intestine plays an important role in first-pass metabolism of dietary carcinogens in the winter flounder.  相似文献   

10.
English sole (Parophrys vetulus) were exposed to environmentally realistic levels of sediment-associated 3H-benzo[a]pyrene (3 μg BaP/g sediment, dry weight) and 14C-Aroclor 1254 (1 μg PCBs/g), separately and together, for up to 10 days. BaP and its metabolites in tissues reached steady-state concentrations by the first day of the exposure, whereas PCBs did not approach steady-state concentrations until the tenth day of exposure. Simultaneous exposure of sole to BaP and PCBs, relative to separate exposure to the xenobiotics, significantly increased the concentrations of BaP-derived radioactivity and decreased the concentrations of PCB-derived radioactivity in some tissues and bile. Accumulation of PCB-derived radioactivity, estimated as the burden in tissues, was significantly greater (4- to 13-fold) than that of BaP-derived radioactivity throughout the experiments and regardless of the type of exposure. The rank of the concentrations of PCB-derived radioactivity in tissues and bile was: bile ～ liver > brain > kidney ～ gill > skin ～ blood ～ muscle and for BaP-derived radioactivity the order was: bile > liver > gill > kidney > skin ～ blood > muscle > brain. BaP-derived radioactivity in liver and bile was present primary (85–99%) as metabolites, whereas PCB-derived radioactivity was present equally as parent compounds and metabolites in bile and primarily (98 %) as parent compounds in liver. Hydrolysis of bile from PCB/BaP-exposed sole with β-glucuronidase/arylsulfatase released 35 % of the BaP-derived radioactivity and 32 % of the PCB-derived radioactivity as primary metabolites. A much higher proportion of the BaP-derived radioactivity (64 %) than the PCB-derived radioactivity (13 %) in bile was unaffected by the enzyme treatment, indicating differences in the conjugation of the primary metabolites of PCBs and BaP. The results suggest that in contaminated environments the tissue to sediment concentration ratios for PCBs would exceed that for BaP and its metabolites; however, BaP would be continually absorbed and metabolized by sole to potentially carcinogenic and mutagenic compounds. In addition, the tissue levels of these toxic compounds may be increased by simultaneous exposure to PCBs.  相似文献   

11.
Benzo[a]pyrene (BaP), a procarcinogenic polycyclic aromatic hydrocarbon (PAH), is bioactivated to BaP diol-epoxides (BPDEs) that can form adducts with DNA and blood proteins. We report here for the first time the in vivo formation of adducts between BPDE and plasma albumin (Alb) from two fish species experimentally exposed to BaP. Brook trout (Salvelinus fontinalis) received either a single i.p. dose (10 mg/kg) or two separate i.p. doses (25 mg/kg; 7 days apart) of BaP, and blood was collected 2 (single exposure) or 3 (multiple exposure) days post-treatment. Arctic charr (Salvelinus alpinus) received 10 i.p. doses (3 mg/kg; a single dose every 6 days), and blood was collected 2 days after the second, sixth, and 10th injections. BPDE-Alb adducts were measured by an improved HPLC/fluorescence method developed to detect and quantify BaP-tetrols released after acid hydrolysis of adducted Alb. HPLC/fluorescence chromatograms of Alb from BaP-treated fish revealed only BaP-tetrol I-1, thus indicating the formation of adducts exclusively via the (+)-anti-BPDE metabolite. Levels of (+)-anti-BPDE-Alb adduct ranged from 0.68 to 19.6 ng of tetrol I-1 per gram of Alb. Notably, adduct level was not related to BaP dose and there was no accumulation of adducts with repeated exposure, which may indicate a very short half-life (< 2 days) of plasma Alb in fish. The data suggest that BPDE-Alb adducts in fish could be useful as a non-destructive biomarker of recent exposure to bioactivated BaP.  相似文献   

12.
Turbot (Scophthalmus maximus) and mussel (Mytilus edulis) microsomes were incubated with DNA to examine if microsomal in vitro metabolism of BaP could result in DNA adducts detected by 32P-postlabelling. Turbot DNA was incubated with benzo[a]pyrene (BaP), NADPH and microsomal activating systems prepared from either livers of unexposed turbot, turbot exposed to BaP or beta-naphthoflavone (beta-NF) or digestive glands from mussels. The beta-NF activating system generated the highest levels of DNA adducts detected in this study (451.7 adducts per 10(8) nucleotides) and were distributed in three discrete adduct TLC spots, one of which (97% of the total adducts) co-migrated with the 32P-postlabelled BaP 7,8-diol, 9,10-epoxide-N2-guanine adduct. Fewer adducts (P < 0.05) were generated by BaP-induced microsomes (9.4-30.6 adducts per 108 nucleotides) but levels were higher (P <0.05) than those generated from untreated fish (3.5 adducts per 10(8) nucleotides). Co-incubation with 500 microM alpha-naphthoflavone (alpha-NF) resulted in 97-99% inhibition in adduct formation implicating cytochrome P450-dependent (CYP) bioactivation however there was some evidence for carry over of BaP in the liver microsomal preparations from BaP injected fish. In contrast to the fish activating systems, no DNA adducts were observed when mussel microsomes were incubated with BaP, DNA and NADPH.  相似文献   

13.
为了了解苯并[a]芘(BaP)对鱼类细胞色素P4501A1(CYP1A1)表达的影响,以褐菖鲉(Sebasticus marmoratus)为实验材料,采用体内实验,研究其在经过不同浓度(0.1、1、10、20、50mg/kg鱼体重量)的BaP诱导后,鱼体肝脏研究CYP1A1基因表达的情况,筛选出后续时间-效应实验中BaP注射的最佳浓度,研究BaP诱导6h、12h、1d、3d、7d后(质量浓度为20mg/kg鱼体重量)鱼体肝脏CYP1A1酶活性、基因表达和蛋白表达的情况。结果表明:剂量-效应实验中,20mg/kg鱼体重量为最佳浓度,此浓度下,基因表达在各组中变化最显著。时间-效应实验中,较空白对照组而言,染毒6h、12h和1d后,EROD酶活性显著增加。3d后开始下降,与对照组相比变化不大,7d后酶活性又发生上调。半定量RT-PCR结果表明,各染毒组与对照组相比,CYP1A1基因表达量都发生了上调,呈现先上升后下降的趋势。其中,6h和12h组相对表达量极显著增加,1d后开始下降且与3d和7d组相比变化不明显。Western blot结果表明,蛋白表达量在染毒12h后表现出显著的诱导效应,随着时间的延长略有回落,但与对照组相比仍有显著性差异。研究表明:BaP对褐菖鲉CYP1A1具有较强的诱导作用。一定质量浓度的BaP注射于褐菖鲉不同的时间后,能诱导褐菖鲉活体EROD酶活性、CYP1A1基因m RNA表达及蛋白表达,并随着时间的延长呈现先诱导后抑制的趋势。这说明BaP作为诱导剂对CYP1A1酶活性和蛋白表达的作用机制可能与调控CYP1A1的转录水平有关。  相似文献   

14.
  • 1.1. The accumulation of aromatic hydrocarbons (AHs) and polychlorinated biphenyls (PCBs) kv English sole (Parophrys vetulus) exposed for up to 108 days to an urban (test) sediment was compared to that for English sole exposed to sediment from a reference area. The concentrations of identified AHs and PCBs in the test sediment were 32 μg/g dry weight and 2·2 μg/g dry weight, respectively. English sole exposed to test and reference sediments for 108 days had biliary concentrations of aromatic compounds fluorescing at BaP wavelengths of 0·6 μg/g, wet weight and hepatic concentrations of PCBs of 1·4 ± 0·6 μg/g wet weight which were ten and eight times, respectively, as great as those in reference sole. These results show that accumulation of AHs and PCBs from sediment by English sole is a significant route of uptake in contaminated environments.
  • 2.2. 3H-benzo(a)pyrene (BaP) and 14C-PCBs were added to the test sediment to compare the uptake and metabolism of BaP to that of PCBs by sole. Steady-state concentrations of 3H-BaP and 14C-PCBs in tissues and fluids were reached by 4 days and 14 days, respectively. At steady state, the level of covalent binding of 3H-BaP to hepatic proteins in test sole was six times greater than that of 14C-PCBs, and there was significantly greater relative formation of BaP-glutathione (GSH) conjugates than PCB-GSH conjugates. Thus, the amount of BaP metabolized to reactive metabolites was greater than that for PCBs, even though the concentration of 14C-PCBs in liver of test sole was five times as great as that of 3H-BaP.
  • 3.3. Trace amounts of 3H-BaP were also added to the reference sediment to determine how simultaneous exposure of English sole to those contaminants already present in the test sediment affected the metabolism and disposition of BaP. The 3H-BaP concentration ratios for liver to sediment and bile to sediment, as well as proportions of biliary BaP-GSH conjugates in test sole, were significantly greater than in reference sole. Thus, the formation and accumulation of potentially toxic metabolites of a carcinogenic AH (BaP) in sole liver were increased by simultaneous exposure to contaminants present in an urban sediment.
  相似文献   

15.
Juvenile turbot (Scophthalmus maximus) were exposed to benzo(a)pyrene (BaP) for 14 d using a glass bead generator flow-through system. Exposure was followed by a recovery period of 16 d. The highest BaP concentration in the edible portion of the fish, 16.5 ± 4.3 μg BaP/kg, was observed on the first day. Then concentrations dropped following first-order kinetics. BaP was below detection level at the end of the experiment. A statistically significant increase in bile fluorescence was observed from day 9 until the end of the experiment, suggesting the elimination of BaP metabolites by this route. No significant differences between control and exposed fish in EROD activity and CYP1A concentration, measured by immunodetection method, were observed. Intraperitoneal injection of 2.5 mg BaP/kg in juvenile turbot induced EROD activity. Under waterborne experimental conditions, bile fluorescence was observed to be a more sensitive biomarker of BaP exposure than EROD activity and CYP1A measurement.  相似文献   

16.
The pollution-tolerant mummichog, Fundulus heteroclitus, inhabits a heavily contaminated estuary, Piles Creek (PC), in Linden, NJ. PC contaminants include PAHs, PCBs and many metals, including high Hg and Pb. PC mummichog livers and kidneys were compared with those from a pristine estuary in Tuckerton (TK), NJ, by standard histopathological methods, with quantification by computerized image analysis. PC livers had>2× the lipid ratios of TK livers. Cell sizes and shapes were not different between populations. TK livers had a 25% incidence of basophilic areas and an age-related 30% incidence of macrophage aggregates; PC livers had none of these lesions. PC livers had a 100% incidence of necrotic foci, compared with 55% of TK livers. Inflammation was noted in 50% of TK livers but only 27% of PC livers. Curiously, the TK livers had a 45% incidence of metacercarial cysts of a digenetic trematode, while none were found in the PC livers. The TK focal necrosis and macrophage aggregates coincided with parasite infestation. There were no observed kidney lesions in either population. Positive biomarkers in this species thus included high hepatic lipid content, possibly necrosis, but no other lesions. The lack of trematode cysts in PC livers may reflect the lack of an intermediate host in this low biodiversity estuary.  相似文献   

17.
The effects of the mammalian inhibitor ellipticine (5,11-dimethyl-[6H]-pyrido[4,3b] carbazole) were examined in a mechanistic study of the cytochrome P450 monooxygenase system of control and β-naphthoflavone (βNF)-induced hepatic microsomes of Platichthys flesus. Ellipticine was indicated to bind to the haem moiety of cytochrome P450s (gave type II binding spectra) and to inhibit the transfer of electrons from both the hydrophobic binding site of cytochrome P450 reductase (P450R) to P450 (inhibited P450R reductase activity) and the hydrophilic binding site of P450R to soluble electron acceptors (inhibited NAD(P)H-cytochrome c reductase activity). No effect was seen on cytochrome b5 reductase activity. Ellipticine inhibition indicated the involvement of (i) P450R (possibly also P450s) in NADPH- but not NADH- dependent hydroxyl radical production, and (ii) electron transfer and P450/P450R interaction in NADPH-dependent cytochrome P450 1A-catalysed monooxygenation (7-ethoxyresorufin O-deethylase activity and benzo(a)pyrene (BaP) metabolism). Differential effects of ellipticine on cumene hydroperoxide (CHP)-dependent BaP metabolism (P450 peroxidase activity) with CHP concentration indicated the existence of at least two forms of P450 with different substrate affinities for CHP, and different mechanisms of formation for protein adducts and free metabolites. Overall, the studies indicate the primary site of action of ellipticine in P. flesus is binding between Fe3+-P450 and P450R.  相似文献   

18.
The dermal absorption of 3H-benzo(a) pyrene (BaP) from sediments of varying organic carbon content was examined in the catfish (Ictalurus punctatus). Test sediments of differing organic carbon concentrations were formulated from natural sediments with the addition of quartz sand to provide organic carbon content of 1.8, 3.7 and 6.1%. Sediments (1.0 g dry wt), spiked with BaP to provide 20.4 μCi at a BaP dose of 75 ng/g, were applied for 6 h to the skin surface (12 cm2) of anesthetized fish. Dermal exposure to BaP in formulated sediments at 6.1, 3.7 and 1.8% resulted in 6-h mass balance bioavailability values of 19.4, 21.9 and 23.2%, respectively. In all treatments, skin in direct contact with sediments had the highest concentration followed by the corresponding muscle layer. Muscle and skin not in direct contact with the labeled sediment had values which averaged 7–580 times lower than the corresponding exposed tissues. Other tissue values ranged from 0.44 pg/g in the heart to 64.21 pg/g in blood. These findings demonstrate appreciable uptake of BaP from surface applied sediments. Within the range examined, varying organic carbon content had a small, but inverse effect upon the dermal bioavailability of BaP.  相似文献   

19.
This study was undertaken to determine the potential for trophic transfer of polycyclic aromatic hydrocarbon (PAH) metabolites from infaunal organisms to bottom-feeding fish. Winter flounder, Pseudopleuronectes americanus, were given single oral doses of ground polychaetes (Nereis virens), either treated with pure [14C]henzo[a]pyrene (BaP) or containing a mixture of naturally produced radiolabeled BaP and BaP metabolites. Fish were sacrificed 24 h after feeding and total accumulated radioactivity and metabolite class profiles determined in major organs. Metabolites produced by worms were absorbed by flounder, although as a percentage of dose given they were less available than parent BaP. Comparison of metabolite profiles in the worm diet and in target organs in the fish indicated that metabolites accumulated through the diet can be further modified by the prey organism and can lead to the formation of bound residues. These results demonstrate that PAH metabolites in the diet are available for accumulation. Furthermore, metabolites absorbed appear to be susceptible to metabolic alteration by consumer organisms.  相似文献   

20.
The role of vitellogenin in the transport of organochlorines was investigated in Atlantic croaker (Micropogonias undulatus) by exposing them through the diet to o,p′-DDT at a concentration of 10.8 μg/100 g fish/day for 14 days or Aroclor 1254 (PCB) at a concentration of 0.5 mg/100 g fish/day for 30 days during gonadal recrudescence. Tissue samples were taken from the fish at various times after initial exposure, and o,p′-DDT and PCBs were extracted in acetonitrile and analyzed by gas chromatography. Analysis of the ovarian tissue collected 2 and 3 weeks from the start of exposure revealed that the o,p′-DDT concentration increases as the gonadosomatic index (GSI) increases (r2 = 0.63), with accumulation ranging from less than 1% to as much as 8% of the total dosage. Interestingly, o,p′-DDT did not accumulate in the testes during the same exposure period. Accumulation of PCBs was found to be 40 times higher in the ovaries than in the testes. Gel filtration of plasma from exposed females showed that o,p′-DDT elutes in the low density lipoprotein and vitellogenin fractions. Control plasma incubated with o,p′-DDT at 4 °C for 16 h followed by chromatography on Sepharose 6B gave similar results with an o,p′-DDT concentration of 0.6μg/mg protein in the vitellogenin fraction. Furthermore, both o,p′-DDT and PCBs were found to bind to purified croaker vitellogenin. These results suggest that lipoproteins, including vitellogenin, are involved in the transport and accumulation of organochlorines in the ovaries of exposed fish.  相似文献   

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