Ethoxyresorufin <9-deethylase induction

SANDERSON J T, AARTS J M M J G, BROUWER A, FROESE K L, DENISON M S and GIESY J P, Comparison of Ah-receptor-mediated luciferase and ethoxyresorufin O-deethylase induction in H4IIE cells implications for their use as bioanalytical tools for the detection of polyhalogenated aromatic compounds , Toxicol Appl Pharmacol 1996 137 316-25. 

The most sensitive effect of in ovo exposures was induction of hepatic ethoxyresorufin O-deethylase (EROD) activity in 1-day-old chicks, with an ED50 dose of 0.312 pg/kg FW egg. 

Sanderson, J.T., S.W. Kennedy, and J.P. Giesy. 1998. In vitro induction of ethoxyresorufin-O-deethylase and porphyrin by halogenated aromatic hydrocarbons in avian primary hepatocytes. Environ. Toxicol. Chem. 17 2006-2018. 

Kennedy, S.W., A. Lorenzen, C.A. James, and R.J. Norstrom. 1992. Ethoxyresorufin-O-deethylase (EROD) and porphyria induction in chicken embryo hepatocyte cultures — a new bioassay of PCB, PCDD, and related chemical contamination in wildlife. Chemosphere 25 193-196. 

The measurement of the ethoxyresorufin-O-deethylase (EROD) activity is another sensitive parameter to detect the effects of paper mill industrial effluents on living organisms in the receiving waters. The EROD activity is a measure of the activity of the cytochrome P-450 enzyme system, which plays a central role in the transformation and elimination of xenobiotics. Increased EROD activity has been shown as far as 40 km from pulp mills, and EROD induction in fish caused by pulp mill effluents remains after biological treatment [60]. It is specified that EROD activity and erythrocytic nuclear abnormalities are induced by abietic and dehydroabietic acid [60]. 

Figure 6.2 Ethoxyresorufin-O-deethylase(EROD) induction in H4IIE rat hepatoma cells exposed to an SPMD dialysate. Four Standard SPMDs were deployed for a 28 day period in Bayou Meto, Arkansas. Doses of dialysate were normalized to gram-equivalents of triolein per mg of cellular protein. This figure was generated by Don Tillitt, USGS-CERC, Columbia, MO, USA and is reprinted with permission from the American Petroleum Institute (Huckins et al., 2002).

Figure 8.6 Induction of significant activity in the ethoxyresorufin-O-deethylase (EROD) screen by an extract of an SPMD sample from Lake Shkodra/Skadar. Reprinted from Rastalletal. (2004a), copyright (2004) reproduced with permission from Environmental Science and Pollution Research.

Abraham, K., R. Krowke, and D. Neubert. 1988. Pharmacokinetics and biological activity of 2,3,7,8-tetrachlorodibenzo-p-dioxin. 1. Dose-dependent tissue distribution and induction of hepatic ethoxyresorufin O-deethylase in rats following a single injection. Arch. Toxicol. 62(5) 359-368. 

Bioassays using induction of the enzymes ethoxyresorufin o-deethylase (EROD) and/or arylhydrocarbon hydroxylase (AHH) in rat hepatoma H-4-IIE cells (Zacharewski et al. 1989) and modified mouse liver cells (Schuman and Hunter 1988) have been developed and tested on water, soil, and fish samples. The... 

Enzyme induction experiments in male and female Wistar rats with administration of TCBT (Ugilec 141) produced a weak increase of total Cytochrome P-450 (< 1.9-fold). Benzhepthamine-AT-demethylase rose up to 3.5-fold, but benzo(a)pyrene hydroxylase (AHH) and ethoxyresorufin-O-deethylase (EROD) inductions were very low. Instead, the latter two inductions were markedly high with TCBT pyrolysate. TCBTs were concluded to be the pheno-barbital (PB) type of inducer, while pyrolysis products contained 3-methyl-colanthrene (3-MC) inducers of the dioxin type. The authors recommended use of TCBTs only in sealed systems [101]. 

Many of the toxic and biological effects induced by polychlorinated dibenzo-p-dioxins and furans (PCDD/Fs) and PCBs such as carcinogenesis, reproductive disturbances and immunotoxic effects are believed to be mediated via the hepatic cytosolic aryl hydrocarbon receptor (Ah receptor) [254,255]. Based on in vitro and in vivo studies, the toxicity of individual organochlorines have been determined relative to 2,3,7,8-tetrachlorodibenzo-p -dioxin (TCDD) and expressed as toxic equivalency factors (TEFs) [254, 256]. In addition to PCDD/F, structurally related PCBs and PCNs bind to the Ah receptor. After binding to the Ah-receptor, the receptor-ligand complex is transferred into the nucleus where it binds to specific DNA sequences and causes transcription of structural genes, which in turn causes synthesis of various cytochrome P4501A1-dependent enzymes such as ethoxyresorufin O-deethylase (EROD) and aryl hydrocarbon hydroxylase (AHH). TEFs for PCNs have been estimated from enzyme-induction assays of EROD and AHH [10, 257] and Luciferase assays in rat cells [12] cf. Table 4. 

The potential toxicity of OH-PCBs was first investigated in the 1970s. Hydroxylated metabolites were reported having higher potencies for cell toxicity than their parent PCBs [64,193]. Phenolic PCB metabolites were also found to affect mitochondrial respiration and the permeability of the inner membrane. The nature of the effect depended on the structure and pKa of the phenolic metabolite [110,194]. Low binding potencies toward the aryl hydrocarbon receptor (AhR), and low induction capacity of ethoxyresorufin-O-deethylase (EROD), respectively, have been reported for phenolic PCB metabolites of non-ortho CB-77 and mono-ortho CB-105 [34, 195]. Dihydroxylated PCBs may be oxidized to quinones that in turn may react with macromolecules to form adducts, and cause oxidative stress leading to cell death [116]. 

Segner, H., A. Behrens, E.M. Joyce, K. Schirmer and N.C. Bols. Transient induction of 7-ethoxyresorufin-O-deethylase (EROD) activity by medium change in the rainbow trout liver cell line, RTL-W1. Mar. Environ. Res. 50 489-493, 2000. 

Tom, D.J., L.E.J. Lee, J. Lew and N.C. Bols. Induction of 7-ethoxyresorufin-o-deethylase activity by planar chlorinated hydrocarbons and polycyclic aromatic hydrocarbons in cell lines from the rainbow trout pituitary. Comp. Biochem. Physiol. 128A 185-198, 2001. 

Sawyer T, Safe S. 1982. PCB isomers and congeners Induction of aryl hydrocarbon hydroxylase and ethoxyresorufin-o-deethylase enzyme activities in rat hepatoma cells. Toxicol Lett 13 87-94. 

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