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1.
The metabolism at specific sites on carcinogenic hydrocarbons such as benzo[a]pyrene (BP) is responsible for activation to the ultimate mutagens and carcinogens, and patterns of metabolism can thus influence the biological effect of such compounds. Marine fish are known to efficiently metabolize BP at the benzo-ring, forming high percentages of the 9,10-dihydrodiol (DHD) and 7,8-DHD, the latter including the penultimate carcinogen.1,2 Hydrocarbon-induced cytochrome P-450 in fish is responsible for initiating metabolism on the benzo-ring, but epoxide hydrolase (EH) activity is required for DHD formation.3,4 Both factors could influence formation of the DHD leading to the ultimate carcinogenic diol-epoxide. In the present study, patterns of BP metabolism were evaluated in a number of individual scup Stenotomus chrysops sampled from local Woods Hole waters, and a correlation is described between variation in the DHD formation and EH activity in these feral fish.  相似文献   

2.
Bivalve and gastropod molluscs readily accumulate polynuclear aromatic (PNAH) and other hydrocarbons from the environment and are widely used in environmental monitoring programmes.1 The response of the cytochrome P-450 monooxygenase or mixed function oxidase (MFO) system to organic xenobiotics is of interest from the comparative viewpoint and in biological effects monitoring.2 We have studied the bivalves Mytilus edulis (mussel) and Cardium edule (cockle) and the gastropod Littorina littorea (periwinkle) exposed to hydrocarbons, experimentally or naturally in the field. The general trend of response in digestive gland microsomes was an increase in cytochrome P-450 content and NADPH-cytochrome c reductase (NADPH-CYTCRED) activity but no increase in benzo[a]pyrene hydrolyase (BPH) activity. Sex and seasonal interactions were evident. We conclude that aspects of the responses may be peculiar to the Mollusc and that NADPH-CTYCRED possibly offers potential for this phylogenetic group as a specific indicator of biological impact by organic pollution.  相似文献   

3.
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   

4.
The prevalence of dermal neoplasia among neotenic tiger salamanders (Ambystoma tigrinum) collected from the Reese Air Force Base sewage lagoon far exceeded that among salamanders from nearby uncontaminated lagoons. Perylene was the predominant pglycyclic aromatic hydrocarbon contaminant in this lagoon. Perylene was shown to be a substrate for monooxygenases in skin and liver homogenates and formed DNA-binding metabolites. Perylene exposure appeared to augment subsequent perylene metabolism by dermal enzymes but it was not a strong inducer of hepatic monooxygenases. Aroclor 1254 induced benzo(a)pyrene and perylene metabolism by both skin and liver enzymes. However, perylene apparently was not activated by salamander enzymes, as suggested by its lack of in vitro mutagenicity and failure to induce tumors.  相似文献   

5.
To examine whether xenobiotics impair teleost reproduction by altering reproductive endocrine function, steroid hormone secretion and ovarian growth were investigated in female Atlantic croaker (Micropogonias undulatus) after chronic oral administration with sublethal doses of three classes of reproductive toxins (lead, benzo[a]pyrene and Aroclor 1254). All the sublethal treatments significantly impaired ovarian growth as assessed by the gonadosomatic index. Reduced ovarian growth was accompanied by a significant decline in circulating 17β-estradiol levels in fish exposed to lead and benzo[a]pyrene. All three toxicants significantly decreased plasma testosterone levels. However, the steroidogenic capacity of ovarian tissue in vitro was not altered by xenobiotic exposure. The data suggest that the decreased ovarian growth in croaker after pollutant exposure may be a consequence of the decline in plasma 17β-estradiol levels. Further, this decrease in circulating levels of gonadal steroids does not appear to be caused by a direct effect of the chemicals on ovarian steroid synthesis.  相似文献   

6.
The disruption of chromosome segregation which is detected visually by the anaphase aberration (aa) test suggests that unequal amounts of DNA are distributed to daughter cells and possibly to subsequent cell generations. To investigate this possibility trout cell cultures and trout embryos (blastodisc) were exposed to benzo[a]pyrene (B[a]P) and the nitrosamide, MNNG, respectively. They were then examined by flow cytometry to determine if anaphase damage resulted in unequal DNA distribution to daughter cells. Both B[a]P and MNNG produced a significant increase (P < 0·01) in aa in cultured cells after 48 h exposure. These values returned to normal by 10 days in the absence of the genotoxic agents, except for the highest concentration (0·5 μg/ml MNNG), which showed only a 50% recovery by that time. Likewise, the coefficient of variation (CV) of nuclear DNA content of the cells also rose significantly after treatment and remained elevated for as long as 14 days following exposure. Experiments with rainbow trout embryos also showed a significant increase in both aa and CV following exposure to MNNG. Flow cytometric analysis of DNA content of trout cells and embryos following exposure to mutagens showed an unequal distribution of DNA that was transmissible through several cell generations. These findings indicate that visible anaphase aberrations could predict heritable genetic defects such as those associated with aneuploidy.  相似文献   

7.
Industrial activities, notably oil and gas industries, are expanding in the Arctic. Most of the biomarkers were developed using temperate organisms living at temperatures above 10 °C. Little is known about the biomarker responses of organisms living between −1.88 and 5 °C. Therefore, assessment of the toxicity of chemicals to cold-water adapted species is required. In this study, the Arctic scallop, Chlamys islandicus, was selected as a key species for bio-monitoring because of wide distribution in Arctic waters and its commercial value. Test animals, stored in seawater at 2 °C, were injected with benzo(a)pyrene (diluted in cod liver oil 5 mg ml−1) in the adductor muscle every 24 h for four days giving a final dose of 0, 74 and 90.6 mg kg−1 wet weight for control, low and high dose, respectively. The biomarkers used were total oxyradical scavenging capacity (TOSC) in the digestive gland and cell membrane stability of haemocytes. TOSC values were significantly reduced (ca. 30%) in exposed groups (P<0.05), indicating a depletion in oxyradical molecular scavengers. The antioxidant defences appeared to be overwhelmed by the reactive oxygen species as the plasma membranes of haemocytes were destabilised (P<0.05) probably due to lipid peroxidation. These data indicate that reactive oxygen species (ROS) were produced by Arctic scallops via the metabolisation of benzo(a)pyrene at 2 °C.  相似文献   

8.
The incidence of hepatoma, epidermal and other forms of cancerous growths in fish is well documented (Halver, 1967; Matsushima & Sugimura, 1976; Dawe et al., 1964). In fish, as in mammals, cancer may be a result of metabolically activated carcinogens. In mammals the primary enzyme system involved in the activation of environmental carcinogens is the cytochrome P-450 linked mixed-function oxidase (MFO). The hepatic microsomes of the species offish studied contain variable levels of cytochrome P-450. Liver microsomes of the trout Salmo trutta lacustris are surprisingly active in metabolising benzo-[a]pyrene (BP) and other compounds preferentially metabolised by polycyclic aromatic hydrocarbon (PAH)-specific cytochrome P-450. This finding may be significant, because it is apparent that the detrimental effects of PAHs require metabolic activation.We have studied the production of reactive intermediates of BP by following their binding to DNA and by measuring the specific nucleotide-BP metabolite complexes by chromatography. Untreated S. trutta liver microsomes catalyse the production of reactive intermediates of BP which bind to nucleotides of DNA at a rate that is 3–4 times higher than that catalysed by control rat liver microsomes. The most prominent DNA-BP metabolite adducts produced by trout liver microsomes are the nucleoside adduct of BP-7, 8-diol-9,10-epoxide and 9-OH-BP-4,5-oxide and other phenol oxides. In contrast to the trout, another fish species, roach (Rutilus rutilus), has extremely low activity. Although the in vitro binding of BP to DNA is not strictly correlated to in vivo binding or biological effects, our results show that reactive intermediates are formed by trout liver and thus the prerequisite for chemical carcinogenesis or mutagenesis is ful filled. This is further supported by the fact that in Ames's test, trout liver preparations produce mutagenic products from promutagens.  相似文献   

9.
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   

10.
苯并(a)芘对紫菜(Porphyra)的致突变效应   总被引：1，自引：0，他引：1  
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11.
The degree of induction of hepatic mixed function oxidase (MFO) enzymes in fish is modulated by environmental conditions. This study was designed to investigate the influence of water temperature, presence or absence of food, and exposure to benzo(a]pyrene (BaP) on the inductive response of bluegill sunfish (Lepomis macrochirus). The results show an increase in 7-ethoxyresorufin O-deethylase (EROD) activity with an increase in acclimation temperature and dose. This activity appears to be associated with a very small fraction of the total cytochrome P-450 induced. Major changes were observed in the 53- and 57-kilodaltons (kDa) electrophoretic bands.  相似文献   

12.
Induction of cytochrome P4501A in fish is a well-known indicator of exposure to polycyclic aromatic hydrocarbons (PAHs) and determination of PAH metabolites in bile by fixed wavelength fluorescence (FF) or synchronous fluorescence spectroscopy (SFS), has become an useful method in monitoring programs. In this work the relationship between cytochrome P4501A (EROD activity) and levels of biliary PAH metabolites was measured in the European eel Anguilla anguilla, in both field and laboratory conditions: organisms were sampled on a seasonal basis from the Orbetello lagoon (Tuscany) to characterize the natural variability of these biological parameters, while in laboratory eels were intraperitoneally injected with benzo[a]pyrene to investigate temporal and dose-dependent induction patterns. Results showed that induction of cytochrome P450 and accumulation of PAHs metabolites in bile are not necessarily correlated either in field, or in laboratory investigations; different seasonal changes were measured in natural conditions and slight variations in dose and time response patterns were also obtained in laboratory exposures.  相似文献   

13.
Indices of hepatic mixed function oxidase (MFO) activity in winter flounder (Pseudopleuronectes americanus) were measured at approximately monthly intervals from November 1983 to October 1985. Benzo[a]pyrene hydroxylase and ethoxyresorufin O-deethylase activities and cytochromes P450 and b5 were generally, but not significantly, higher in males than in females. The MFO activity varied seasonally, reaching a maximum during or shortly after spawning. Variation in MFO enzyme activity between sexes was never greater than 2-fold at any time, and within sex, no greater than 6-fold during the seasonal cycle. This variability is less than that caused by exposure to environmentally realistic levels of some pollutants; measurements of MFO activity in this species might therefore be used to indicate environmental contamination.  相似文献   

14.
Macoma inquinata, a detritus feeding clam, was exposed for 60 days to coarse-grained, and Abarenicola pacifica, a burrowing polychaete, to fine-grained, sediment. Each sediment contained 14-C-labelled phenanthrene, chrysene or benzo(a)pyrene. Over 70% of the chrysene and benzo(a)pyrene, but only 8% of the phenanthrene, remained in the coarse sediment during the exposure. Essentially all of the chrysene and benzo(a)pyrene and 70% of the phenanthrene remained in the fine sediment. The concentrations of chrysene and benzo(a)pyrene in the clams rose steadily, reaching levels 11·6 and 5·2 times as high as those in the sediment. The tissue phenanthrene concentration rose for 3 days, then fell to one-eighth of the initial concentration. The concentrations of each of the aromatic hydrocarbons in Abarenicola tissue increased for 2 weeks to four to six times the sediment levels. The tissue concentration of chrysene remained constant thereafter, but the levels of phenanthrene and benzo(a)pyrene fell to three-quarters of their peak values. No intermediate degradation products of any of the hydrocarbons were identified in extracts of sediment from either exposure system, or in solvent extracts of tissue or of tissue digestates.Significant 14C-activity, associated with non-solvent extractable compounds, remained in tissue digestates of individuals of both species exposed to phenanthrene.  相似文献   

15.
In fish, as well as in mammals, it is well known that the cytochrome P450-dependent oxidative metabolism of xenobiotics can generate DNA-reactive species. Moreover, this metabolism is known to be inducible by several compounds of environmental significance, such as polychlorobiphenyls, polycyclic aromatic hydrocarbons (PAHs) and dioxins. Consequently, we studied the relationship between the degree of induction of the cytochrome P4501A, expressed as that of 7-ethylresorufin O-deethylase (EROD) activity, and the level of DNA-adducts, using the post-labelling assay, in the liver of rainbow trout exposed to benzo(a)pyrene (a representative PAH). The results showed a significant 2- to 4-fold increase in EROD activity 2, 4 and 8 days after treatment, paralleled by an increase in DNA-adduct levels. This work further emphasizes the involvement of cytochrome P4501A in the metabolism of benzo(a)pyrene into genotoxic metabolites in rainbow trout.  相似文献   

16.
Stress proteins (heat shock proteins, hsps) form part of the cellular protein repair system, and are induced by a wide variety of Stressors. To determine their suitability as tools for assessing sublethal sediment toxicity, we measured levels of members of the stress protein families hsp60 and hsp70 in benthic estuarine amphipods (Ampelisca abdita) exposed to sediments from 23 different sampling sites in San Francisco Bay for 10 d. Concentrations of sediment-associated xenobiotics were determined. Per cent survival was recorded and surviving animals were analysed for stress proteins using western blotting techniques. An inverse correlation (r2 = 0.44) was seen between amphipod survival and hsp64 levels, and hsp64 levels were positively correlated with concentrations of total polycyclic aromatic hydrocarbons (PAHs) (r2 = 0.5). Principal component analysis revealed that amphipod mortality was linked to a combination of several PAHs (phenanthrene, fluoranthene, pyrene, benzo(a)pyrene) and di-n-butylphthalate at southern San Francisco Bay sites. At northern San Francisco Bay sites, negative correlations were found between hsp64 levels and organotin compounds (MBT, DBT, TBT), and between hsp71 levels and the PAHs, benzo (b,k)fluoranthene and benzo(G,H,I)perylene, suggesting an inhibitory effect of these compounds on stress protein expression.  相似文献   

17.
Purification of cytochromes P-450 from liver microsomes of β-naphthoflavone (BNF)-fed rainbow trout yielded three apparently homogeneous forms. The major form (LM4b)* appears to be a P-448 type of cytochrome. A minor form (LM4a), having properties very similar to LM4b, was also obtained. In addition, a P-450 form (LM2) was isolated, with properties quite different from LM4a or LM4b, including a high rate of aflatoxin B1 (AFB1) metabolism (Williams & Buhler, 1983c). Antibodies to all three forms were obtained from rabbits. The IgGs prepared against LM4a and LM4b both cross-reacted (forming lines of identity) equally well with both antigens on Ouchterlony plates. Rat P-448 cross-reacted (without lines of identity) with both LM4a- and LM4b-IgG. LM4b-IgG was much more effective than LM4a-IgG for inhibition of LM4a or LM4b reconstituted benzo[a]pyrene (BP) hydroxylase, suggesting that these two antibodies recognize different antigenic sites. The LM2-IgG did not cross-react with any of the other rat or trout cytochromes P-450 examined. Levels of LM2 and LM4b in microsomes from untreated, polychlorinated biphenyl (PCB), phenobarbital (PB) or BNF-treated trout were estimated with an immunological technique involving electrophoresis on SDS-PAGE, followed by transfer to nitrocellulose and staining with either LM 2 - or LM4b -IgG. The ratio of in microsomes from PCB- or BNF-treated rainbow trout was much higher than 1, whereas the reverse was true with microsomes from untreated rainbow trout. These results are consistent with previous observations (Vodicnik et al., 1982) that pretreatment with BNF induced the synthesis of a P-448 type cyytochrome, presumably responsible for the great increase in the metabolism and activation of BP seen in these fish. Conversely, pretreatment with PB did not affect the levels of either LM2 or LM4b. This specific immunological technique should make it possible to assay the levels of these P-450 and P-448 isozymes in various strains of rainbow trout and other species of fish. In addition, the effect of age, sex, diet and exposure to P-450 and P-448 inducers could be examined and, perhaps, utilized to predict the relative risk of certain populations to pollutants activated by these different isozymes.  相似文献   

18.
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   

19.
Haemocytes play an essential role in the internal defence of molluscs. It has been reported that organic xenobiotics commonly found as pollutants in the marine environment impair defence capabilities of haemocytes. The purpose of the present study was to investigate the effects of benzo(a)pyrene [B(a)P] on the integrity of the actin cytoskeleton and on endocytosis in haemocytes and to see if these effects are related to generation of reactive oxygen species. Haemocytes were exposed in vitro to B(a)P (0.5–40 μg/ml) for 1 h. Cell viability (using 2,3-bis[2-methoxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxanilide or XTT assay) indicated that selected doses were sublethal. Uptake of neutral red was significantly decreased in a dose-dependent manner in B(a)P-treated haemocytes. Distribution of actin filaments, labeled with rhodamine-conjugated phalloidin, was altered in haemocytes treated with 20 or 40 μg/ml B(a)P. These effects could be related to an increased production of superoxide anion during B(a)P metabolism, as detected by the nitroblue tetrazolium (NBT) reduction assay in haemocytes treated with 10 μg/ml B(a)P.  相似文献   

20.
This paper reports a rapid and facile procedure for obtaining of DNA from small, whole aquatic organisms (fathead minnow, Pimephales promelas) as well as from the liver of another species (bluegill sunfish, Lepomis macrochirus) and the subsequent estimation of its double strandedness. DNA was isolated from various tissues by homogenization in a basic pH solution containing detergent followed by differential extraction using organic solvents. Additional purification was accomplished by molecular sieve chromatography. Under defined alkaline unwinding conditions, the amount of double-stranded and single-stranded DNA was determined using the bisbenzimidazole dye Hoechst 33258. The technique was used to detect the occurrence of strand breaks in DNA of fathead minnows chemically exposed to benzo[a]pyrene.  相似文献   

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