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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.
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   

4.
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   

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 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   

6.
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   

7.
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   

8.
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   

9.
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   

10.
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   

11.
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   

12.
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   

13.
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   

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.
Previous experiments demonstrated that exposure of mummichog to cadmium (Cd) in combination with benzo[a]pyrene (BaP) caused a higher mortality than would be expected from simple additive effects. Experiments are described here that investigated whether BaP exposure inhibits the induction of metallothionein (MT), a major detoxifying protein for Cd, or if reactive BaP metabolites compete with Cd for binding sites on MT. Fish were injected with or without BaP (18 mg/kg) in combination with a low (1 mg/kg) or high (3.2 mg/kg) dose of Cd, and in one treatment BP was dosed 4 days after Cd. The results showed a rapid induction of MT to 1.5 mg/g wet weight liver, 1 day after injecting the low Cd dose. Simultaneous BaP exposure significantly delayed the induction of MT, for both low and high Cd doses, and BaP temporarily lowered the induced MT concentration when dosed 4 days after induction by Cd. To test if binding of BaP metabolites to MT reduces the detoxification potential for Cd, microsomes of CYP1A-induced fish were incubated with MT and radiolabeled BaP. Active metabolism of BaP was observed by high-performance liquid chromatography analysis, but no association of BaP metabolites with MT was found. Neither could this be demonstrated in vivo, in liver MT isolated from mummichog dosed with 3H-BaP and Cd. These results suggest that increased toxicity of Cd in combination with BaP exposure is likely to be caused by inhibited MT synthesis, rather than by interference of BaP metabolites with Cd binding on MT.  相似文献   

16.
在实验生态条件下,观察苯并(a)芘、芘及其等浓度混合物暴露对梭鱼(Mugil so-iuy)肝脏谷胱甘肽硫转移酶(GST)活性的影响。结果显示,在7d的暴露中,苯并(a)芘、芘对肝脏GST活性的影响主要为诱导效应,芘对GST活性的诱导比苯并(a)芘强。混合物在15d的暴露中未观察到GST活性的诱导,而是在暴露的后期出现GST活性的抑制。实验表明,肝脏GST活性的诱导指示受到PAHs污染胁迫,而GST活性抑制则是受到较长时间或较严重的污染。  相似文献   

17.
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   

18.
Our goal was to study the involvement of cytochrome P450 genes in estrogen metabolism and the extent to which the potentially carcinogenic 4-hydroxyestradiol metabolite is formed by channel catfish (Ictalurus punctatus; CC). Estradiol metabolism and ethoxyresorufin-O-deethylase (EROD) activity were assessed in several tissues from fish collected from three variably contaminated sites in the Mississippi River Delta, from laboratory control fish, and from fish exposed to 20 mg/kg benzo(a)pyrene (BaP) i.p. for 4 days. Liver EROD activity was induced by BaP, but Delta fish EROD activities were not statistically higher than activities in control fish. Gill microsomal EROD activity was also induced by BaP, but activities were 8- to 77-fold lower than those from liver. The predominant estrogen metabolites formed by CC liver, gill and gonad microsomes were 2-hydroxyestradiol and estrone as detected by GC/MS. Liver and gill 2-hydroxyestradiol formation was induced in BaP-dosed fish. The trends in hydroxyestradiol formation in field collected fish were more variable. In all fish liver microsomes there was more 2- compared to 4-hydroxyestradiol formed. However, BaP-treatment increased the 4:2 hydroxyestradiol ratio from 0.04 in control fish to 0.2 in BaP-exposed fish, suggesting that BaP induces the formation of the potentially genotoxic estrogen metabolite. No detectable 4-hydroxyestradiol was produced by gill and gonad microsomes. These results will ultimately help in determining which fish P450 genes are susceptible to environmental contamination and may be involved in estrogen genotoxicity.  相似文献   

19.
Despite the fact that BaP is a carcinogen, mammalian immunosuppressant, and ubiquitous aquatic pollutant, knowledge regarding the effects of BaP on the immune system of fish is still lacking. To begin to fill this gap, studies were conducted in medaka to examine the effects and mechanisms by which BaP exposure might alter host immunocompetence. Fish, exposed by IP injection of BaP (2-600 microg/g BW), were examined after 48 h for effects upon immune function and CYP1A expression/activity. Benzo[a]pyrene, at a concentration below that which increased levels of CYPIA expression/activity (2 microg BaP/g BW) suppressed lymphocyte proliferation. Concentrations of BaP at 20 and 200 microg/g BW. suppressed antibody-forming cell (AFC) numbers, superoxide production, and host resistance against bacteria. In contrast, exposure to the low affinity aryl hydrocarbon receptor (AhR) agonist, benzo[e]pyrene (BeP), neither induced CYP1A expression nor altered immune function. Given the lack of immunosuppressive effects produced by BeP, and the fact that exposure to the AhR antagonist (and CYP1A inhibitor) alpha-naphthoflavone (ANF) ameliorated the suppressive effects of BaP upon AFC numbers, the AhR pathway (including CYP1A-mediated production of reactive BaP metabolites) appears important in mediating BaP-induced immunotoxicity in fish, as in mammals. In the past, the medaka has proven a successful model for assessing carcinogenic agents. These studies have demonstrated its utility for also determining the immunosuppressive effects of an important aquatic contaminant.  相似文献   

20.
The viviparous blenny (Zoarces viviparus), also known as eelpout, is considered a suitable biomonitor for use in European estuarine and coastal waters. We have previously shown that Z. viviparus from the industrialised Tyne estuary (UK) display certain histopathologies (e.g., ovotestis and hepatic nuclear and cellular pleomorphism), which are associated with contaminant exposure [Mar. Environ. Res. 55 (2003) 137]. Furthermore, the prevalence of these pathologies was higher than in fish collected from a less contaminated reference site (the Alde estuary, UK). Here, tissue samples were collected from Z. viviparus from the Tyne and Alde estuaries (in the spring and autumn) and analysed for DNA adducts using the (32)P-postlabelling assay and for histopathology. Z. viviparus caught from the Tyne during the spring (56.4+/-18.5 adducts per 10(8) nucleotides) and autumn (63.1+/-7.5 adducts per 10(8) nucleotides) exhibited patterns of DNA adducts which indicated exposure to a complex mixture of genotoxins. In contrast, levels of DNA adducts in Z. viviparus from Alde estuary were significantly lower during both sampling periods. Histopathological changes to the gonads included intersex (ovotestis) and germ cell apoptosis (detected via the TUNEL assay) in male fish captured from the Tyne estuary. Further studies on the use of germ cell apoptotic rate at different estuarine sites are required if it is to be used as a reproductive biomarker of contaminant exposure in male fish.  相似文献   

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