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- James, M. O., et al.
(författare)
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Properties and regional expression of a CYP3A-like protein in channel catfish intestine
- 2005
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Ingår i: Aquatic Toxicology. - : Elsevier BV. - 0166-445X. ; 72:4, s. 361-371
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Tidskriftsartikel (refereegranskat)abstract
- Biotransformation in the intestine may influence the bioavailability and toxicity of ingested xenobiotics. The objective of this study was to examine the expression and catalytic properties of a constitutive cytochrome P450 (CYP) 3A-like protein along the intestine of channel catfish, Ictalurus punctatus. Fish were maintained on commercial chow or nutritionally complete semi-purified diets. Polyclonal antibodies generated against rainbow trout CYP3A proteins reacted strongly with catfish washed intestinal microsomes on Western blots showing a major protein band with MW of 59 kDa. In catfish maintained on a standard chow diet, the expression of this protein was higher in the proximal segment (0.101 ± 0.031 units/mg protein, mean ± S.D., n = 4) than in the distal part (0.032 ± 0.023 units/mg protein). Microsomal testosterone 6β-hydroxylation activity was monitored as the catalytic indicator of CYP3A, and was higher in proximal than distal catfish intestine (263 ± 80.3 and 88.6 ± 15.6 pmol/min/mg protein for proximal and distal, respectively, mean S.D., n = 4). CYP3A protein levels and testosterone 6β-hydroxylation activities were lower in microsomes from the proximal segment of intestine from catfish maintained on a semi-purified diet, compared with commercial chow, but again the proximal intestine had higher CYP3A and 6β-hydroxylase activities than distal intestine. Testosterone 6β-hydroxylase activities in all samples correlated with the CYP3A protein levels, r(2) = 0.8. Testosterone 6β-hydroxylation was inhibited by specific CYP3A inhibitors, ketoconazole (IC50 = 0.02 μ M) and erythromycin (IC50 = 41 μ M), as well as general CYP inhibitors, metyrapone (IC50 = 2.8 μ M) and SKF-525A (IC50 = 25 μ M). There was evidence for the involvement of CYP3A in the mono-oxygenation of benzo(a)pyrene and of (-)-benzo(a)pyrene-7,8-dihydrodiol in intestinal microsomes from catfish maintained on the semi-purified diet. Mono-oxygenation of both substrates was increased in a concentration-dependent manner by in vitro addition of a-naphthoflavone. Benzo(a)pyrene hydroxylase activities were higher in proximal than in distal intestine; 3.72 ± 0.77 pmol/min/mg protein, mean ± S.D., n = 5 and 1.45 ± 0.42 in these respective segments. The results of this study strongly suggest that CYP3A is important in the first pass metabolism of dietary xenobiotics in untreated fish. © 2005 Elsevier B.V. All rights reserved.
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| 5. |
- Rosendahl, Ann, et al.
(författare)
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Systemic IGF-I administration stimulates the in vivo growth of early, but not advanced, renal cell carcinoma.
- 2008
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 123, s. 1286-1291
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Tidskriftsartikel (refereegranskat)abstract
- Insulin-like growth factor I (IGF-I) is a potent mitogen and antiapoptotic factor. Although elevated serum IGF-I levels have been associated with increased cancer risk, it is not yet clear whether IGF-I sensitivity is sustained throughout tumor progression. To evaluate the biological effects of IGF-I during renal cell carcinoma (RCC) establishment and progression, we administered recombinant human IGF-I to severe combined immuno-deficient mice bearing early or more established Caki-2 human RCC tumors. IGF-I significantly enhanced the tumor growth 2.4-fold when administered early after tumor inoculation. This IGF-I-induced growth was accompanied with enhanced tumor cell proliferation, tumor vascularization, as well as increased intratumoral insulin-like growth factor binding protein 3 (IGFBP-3) and pSmad2 levels. In contrast, IGF-I administrated to more established RCC tumors showed no effect on tumor growth, with subsequently much lower Ki-67, IGFBP-3 and pSmad2 levels. Taken together, these data suggest that systemic IGF-I has potent actions during early RCC tumor development with a sustained long-term effect on proliferation and neovascularization although with progression, later tumors appear to become desensitized to systemic IGF-I effects. (c) 2008 Wiley-Liss, Inc.
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| 6. |
- Schlenk, D., et al.
(författare)
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Biotransformations : Biotransformations
- 2008
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Ingår i: The Toxicology of Fishes. (Eds. R. Di Giulio and D. Hinton). - : CRC Press Taylor & Francis Group. - 9780415248686
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 7. |
- Stephensen, Eiríkur, et al.
(författare)
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Biomarker responses and chemical analyses in fish indicate leakage of polycyclic aromatic hydrocarbons and other compounds from car tire rubber
- 2003
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Ingår i: Environmental Toxicology and Chemistry. - : Wiley. - 0730-7268 .- 1552-8618. ; 22:12, s. 2926-2931
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Tidskriftsartikel (refereegranskat)abstract
- Rubber tire material contains toxic compounds including oils rich in polycyclic aromatic hydrocarbons (PAH), so-called highly aromatic (HA) oils, as well as other reactive additives used as antioxidants, antiozonants, and vulcanization accelerators. The toxicity of rubber tire leachates to aquatic organisms has been demonstrated before. However, previous Studies have focused on lethal rather than sublethal effects. We kept rainbow trout (Oncorhynchus mykiss) in tanks with two types of fires: a tire containing HA oils in the tread or a tire free of HA oils in the tread. After 1 d of exposure. an induction of cytochrome P4501A1 (CYP1A1) was evident in both exposed groups, measured as elevated ethoxyresorufin-O-deethylase (EROD) activity and increased CYP1A1 mRNA levels. After two weeks of exposure, EROD activity and CYP1A1 mRNA were still high in fish exposed to leachate from HA oil-containing tire, whereas the effect was somewhat lower in fish exposed to leachate from HA oil-free tread tire. Compounds in the tire leachates also affected antioxidant parameters. Total glutathione concentration in liver as well as hepatic glutathione reductase, glutathione S-transferase, and glucose-6-phosphate dehydrogenase activities were markedly elevated after two weeks of exposure in both groups. The responses were greater in the group exposed to leachate from HA oil-free tread tire. Vitellogenin measurements did not indicate leakage of estrogenic compounds from the tires. Chemical analyses of bile from exposed fish revealed the presence of hydroxylated PAH as well as aromatic nitrogen compounds indicating uptake of these compounds by the fish.
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