Rat liver cytochrome P-450 isozymes as catalysts of aldrin epoxidation in reconstituted monooxygenase systems and microsomes

Wolff, Thomas; Guengerich, F. Peter

doi:10.1016/0006-2952(87)90535-1

Cited by 35 publications

(11 citation statements)

References 21 publications

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“…This is revealed by the relative activities of certain substrates following the ethanol-feeding regimens. For example, the specific activity of aldrin epoxidase is known to be induced by phenobarbital (43,49,50). The data shown in Table 4 is consistent with that assertion.…”

Section: Discussionsupporting

confidence: 87%

“…To further understand the different induction patterns resulting from ethanol and PB treatment, aldrin epoxidase was studied as a function of ethanol ingestion in the HF and LF diets. In agreement with the findings of Wolff and Guengerich (43), PB and Aroclor increased the specific activity of aldrin epoxidase over controls 2.4-fold and 1.9-fold, respectively, without increasing the turnover number ( Table 4). The specific activity and turnover number of microsomal aldrin epoxidase were decreased 37% and 62%, respectively, by 3-MC treatment relative to the control (Table 4).…”

Section: Effects On Aldrin Epoxidasesupporting

confidence: 91%

“…Aldrin epoxidase has been used as a probe to detect cytochrome P-450 isoenzymes characteristic of PB induction in male Sprague-Dawley rats (43). To further understand the different induction patterns resulting from ethanol and PB treatment, aldrin epoxidase was studied as a function of ethanol ingestion in the HF and LF diets.…”

Section: Effects On Aldrin Epoxidasementioning

confidence: 99%

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Alteration of liver microsomal monooxygenases and substrate competition with aniline hydroxylase from rats chronically fed low‐fat and high‐fat‐containing alcohol diets

Winston

Narayan

1988

J. Biochem. Toxicol.

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Male Sprague-Dawley rats fed ethanol (EtOH) 36% of total calories for four weeks in a liquid diet containing either 34% (HF) or 12% (LF) of calories as fat were studied with respect to induction of microsomal monooxygenases (MFO) and substrate competition with EtOH-inducible aniline hydroxylase. The specific activity and turnover of aniline hydroxylase were induced to similar extents by HF-EtOH and LF-EtOH diets. Whereas, both LF-EtOH and HF-EtOH caused a decrease in the turnover of arylhydrocarbon (benzo[a]pyrene) hydroxylase (AHH) and aldrin epoxidase compared to pair-fed (PF) controls, LF-EtOH but not HF-EtOH increased the turnover of ethoxycoumarin and ethoxyresorufin O-deethylase (ECOD and EROD). The increase in ECOD and EROD and the decrease in AHH by EtOH is contrary to the parallel induction of these activities by 3-methylcholanthrene (3-MC) and Aroclor 1254 (Aroclor). Benzo(a)pyrene (BaP) stimulated aniline hydroxylase in the HF-EtOH and PF systems, whereas with LF diet, stimulation was seen only in the EtOH group. Ethoxycoumarin (EC) inhibited aniline hydroxylase by microsomes from EtOH- and pyrazole-treated rats, whereas it stimulated aniline hydroxylase by control microsomes, suggesting that the EC effects were associated with EtOH-inducible cytochrome P-450. Ethoxyresorufin (ER) inhibited aniline hydroxylase in EtOH and PF groups, thus the differential effects of EC were not nonspecific O-deethylase effects. The effects of EtOH feeding on ECOD, EROD, and AHH (ie, substrates for 3-MC-inducible cytochrome P-450) displayed a greater differential between the experimental and control group with the LF- than with the HF-containing diet. The findings suggest that the alteration of certain MFO activities by chronic EtOH ingestion can be modified by the content of dietary fat. Moreover, the competition dynamics of MFO substrates toward EtOH-inducible aniline hydroxylase are altered by EtOH feeding and, in turn, modified by dietary fat.

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Section: Discussionsupporting

confidence: 87%

Section: Effects On Aldrin Epoxidasesupporting

confidence: 91%

Section: Effects On Aldrin Epoxidasementioning

confidence: 99%

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Alteration of liver microsomal monooxygenases and substrate competition with aniline hydroxylase from rats chronically fed low‐fat and high‐fat‐containing alcohol diets

Winston

Narayan

1988

J. Biochem. Toxicol.

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“…6), suggesting that the PROD activity detected here is catalyzed primarily by CYPIA. Similarly, aldrin epoxidase activity was found to be very low in short-finned pilot whale, striped dolphin, and killer whale, compared to that in rat (Watanabe et al, 1989); this activity is catalyzed largely by PB-inducible CYP2B forms in rat (Wolff and Guengerich, 1987). The in vitro production of a K-region BP metabolite (4,5-dihydrodiol) by beluga (Fig.…”

Section: Cytochrome P4502bmentioning

confidence: 99%

Tetrachlorobiphenyl metabolism, toxicity, and regulation of cytochrome P50 expression in a marine teleost fish

White¹

1994

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The effects of 3,3',4,4'-tetrachlorobiphenyl (TCB) were examined in the marine fish scup (Stenotomus chrysops), focusing on the interactions between TCB and the CYP1A1 enzyme system. A low TCB dose (0.1 mg/kg) elicited strong and sustained induction of hepatic CYPlA1 mRNA, protein content, and catalytic activity. A high TCB dose (5.0 mg/kg) elicited similar, strong induction of hepatic CYPlA1 mRNA, but not of CYPlA1 protein content or catalytic activity. This post-transcriptional "suppression" at the high TCB dose was specific for CYPlA1, and was not seen with other hepatic enzymes. In vitro studies indicate that hepatic microsomal CYP A1 is inactivated in the presence of TCB plus cofactor, likely due to the production of reactive oxygen species during TCB occupation of the active site. CYPlA1 inactivation by TCB in vitro may explain the TCBelicited suppression of CYPlA1 protein content in vivo.Both TCB doses elicited strong CYPlA1 induction in vascular endothelium of all organs, which was sustained for several weeks. Induction in intestinal epithelia was stronger at the high TCB dose, but induction in epithelia of liver, kidney, and gill were stronger at the low TCB dose. Both TCB doses caused proliferation of endoplasmic reticulum in liver, renal tubule necrosis, depletion of hematopoietic tissue in kidney, hyperplasia of gill epithelia, and increased number of melanomacrophage aggregates in spleen. The high dose induced tail fin erosion, affecting both epithelial and calcified bone tissue. Tissue alterations were more severe at the high TCB dose, and repair of lesions occurred by day 16 at the low dose. The high dose caused mortality of many individuals.The two TCB congeners 3,3',4,4'-TCB and 2,2',5,5'-TCB were each converted to aqueous-soluble metabolites by hepatic microsomes from scup, beluga whale, and pilot whale. Induction response, correlation analysis, and inhibition studies indicate that 3,3',4,4'-TCB is metabolized by scup CYP1Al, and 2,2',5,5'-TCB by the putative scup CYP2B. Correlation analysis and inhibition studies suggest that 3,3',4,4'-TCB is metabolized by cetacean CYP1A. Both cetacean species expressed microsomal proteins that are immunochemically related to mammalian CYP2B forms. Cytochrome P450 systems from both cetacean species are partially characterized here.

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“…The ISO common name definition of dieldrin therefore refers to only the exo form. These differences have found little attention in the literature, as even the Environmental Health Criteria on aldrin and dieldrin (WHO, 1989) does not mention either the different configurations of dieldrin or that the endo and exo forms can be produced under environmental and biological conditions (Wolff and Guengerich, 1987).…”

Section: Introductionmentioning

confidence: 99%

Opinion of the Scientific Panel on Plant protection products and their Resi-dues on a request from the Commission on the risks associated with an in-crease of the MRL for dieldrin on courgettes

2007

EFSA Journal

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SUMMARYFollowing a request from the European Commission, the Panel on Plant Protection Products and their Residues (PPR Panel) was asked to deliver a scientific opinion on the risks associated with an increase of the MRL for dieldrin on courgettes.Dieldrin was developed in the 1940s and was widely used as an insecticide up to the early 1970s. However, its use was stopped when it became clear that it has very unfavourable environmental and toxicological characteristics. Today, dieldrin is therefore banned in most countries of the world. Moreover, it is on the list of the Stockholm Convention to protect human health and the environment from persistent organic pollutants.Dieldrin is very persistent in the environment and has a strong potential to accumulate in the food chain. Due to the very slow environmental degradation of the substance, dieldrin is still a widespread soil contaminant in Europe and other places. When growing courgettes on such soils, residues can be taken up by the plants and transported to the fruits. Monitoring data from The Netherlands show that courgettes grown in greenhouses from the western part of the country do not always comply with the existing MRL of 0.02 mg/kg. The Netherlands has therefore requested an increase of this MRL-value to 0.05 mg/kg and the European Commission has asked EFSA to evaluate the toxicological implications of the proposed new MRL-value.The main reasons for prohibiting the active substance were its environmental persistence and its tendency to accumulate in animal tissues. It is therefore appropriate to ask whether exposure as a result of eating courgettes with an increased MRL, together with other known sources of exposure (e.g. through animal products), represents a potential risk for European consumers in the long as well as in the short term.The residue definition for dieldrin under current EU residue guidelines specifies dieldrin "singly or combined with aldrin, expressed as dieldrin". This definition reflects the close chemical and toxicological relationship between these two cyclodiene insecticides. There are two isomers of dieldrin, the exo-and the endo-form. Dieldrin itself is the exo-isomer. The PPR Panel 2 briefly reviewed the characteristics of the different isomeric forms of dieldrin and concluded that focus should be on the exo-form of the substance, i.e. dieldrin itself. The Panel agreed not to include photodieldrin -an environmental product of dieldrin -in further consideration because this substance is not included in the residue definition. Furthermore photodieldrin has not been studied in such detail and the literature and data on the occurrence and fate of its residue are scarce.The Joint FAO/WHO Meeting on Pesticide Residues (JMPR) established an acceptable daily intake (ADI) for dieldrin in 1967, confirmed this in 1977 and converted (but not re-evaluated) it to a PTDI (Provisional Tolerable Daily Intake) in 1994. JMPR has not derived an acute reference dose (ARfD) for dieldrin. The propensity of dieldrin to accumulate in biological organisms...

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Rat liver cytochrome P-450 isozymes as catalysts of aldrin epoxidation in reconstituted monooxygenase systems and microsomes

Cited by 35 publications

References 21 publications

Alteration of liver microsomal monooxygenases and substrate competition with aniline hydroxylase from rats chronically fed low‐fat and high‐fat‐containing alcohol diets

Alteration of liver microsomal monooxygenases and substrate competition with aniline hydroxylase from rats chronically fed low‐fat and high‐fat‐containing alcohol diets

Tetrachlorobiphenyl metabolism, toxicity, and regulation of cytochrome P50 expression in a marine teleost fish

Opinion of the Scientific Panel on Plant protection products and their Resi-dues on a request from the Commission on the risks associated with an in-crease of the MRL for dieldrin on courgettes

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