Disease relevance of C13630

• ICZ has a Kd of 190 pM for aromatic hydrocarbon responsiveness-receptor binding and an EC50 of 269 nM for induction of cytochrome P4501A1, as measured by ethoxyresorufin O-deethylase activity in murine hepatoma Hepa 1c1c7 cells [1].
• In concordance, total CYP1A1 activity, as measured by the ethoxyresorufin O-deethylase assay, was detected in mitochondrial, nuclear, and microsomal fractions of ovarian cancer cells but was notably absent in all subcellular fractions of HOSE cells [2].
• Finally, P450 1A2 and 1A2-supported ethoxyresorufin O-deethylase activity were significantly reduced in hepatic microsomes from patients with both types of advanced liver disease [3].
• The expressed protein from E. coli membranes had a CO-binding spectrum typical of P450s, and it catalyzed the O-dealkylation of the CYP1A prototype substrates ethoxyresorufin and methoxyresorufin [4].
• We determined if individual PAHs and other procarcinogens affect the activities of human P450s 1A1, 1A2, and 1B1 by measuring 7-ethoxyresorufin O-deethylation (EROD) activity and metabolic activation of PAH dihydrodiols and 2-amino-3,5-dimethylimidazo[4,5-f]quinoline (MeIQ) to genotoxic metabolites in a Salmonella typhimurium NM2009 system [5].

High impact information on C13630

• The induction of cytochrome P450 1A1 transcripts by WY-14643 was associated with a marked increase of ethoxyresorufin O -deethylase activity (10-fold at 200 mumol/L) [6].
• P450-dependent enzymatic activity was assessed by deethylation of ethoxyresorufin [7].
• Of the mutations made, the substitution of Trp-676 with alanine (W676A) resulted in a functional NADH-dependent enzyme, which catalyzed the reduction of cytochrome c and ferricyanide as well as facilitated the metabolism of 7-ethoxyresorufin by CYP1A2 [8].
• Clotrimazole (0.7 microM) and 7-ethoxyresorufin (1 microM), both considered to be specific inhibitors of the cytochrome P-450 monooxygenase enzymes, inhibited the vasodilator effect, suggesting that AA-induced renal vasodilation is mediated by one or more cytochrome P-450-derived AA metabolites [9].
• Curcumin increased both expression (reverse transcription-PCR analyses) and function (high-performance liquid chromatography determination of ethoxyresorufin metabolism) of cytochrome P-450 (CYP) 1A1 and/or CYP1B1 [10].

Chemical compound and disease context of C13630

• We determined the effect of indirubin in MCF-7 breast cancer cells on induction of the activities of cytochromes P450 (CYP) 1A1 and 1B1, as measured by estradiol and ethoxyresorufin metabolism, and on induction of the CYP1A1 and CYP1B1 mRNAs [11].
• The statuses of CYP1A1 and 1B1 in UW228-3 medulloblastoma cells without and with resveratrol treatments were elucidated in this study with ethoxyresorufin O-deethylation assay, followed by RT-PCR, immunocytochemical staining and Western blot hybridization [12].
• In a natural outbreak of this disease in our institution we demonstrated that mouse hepatitis virus appears to have little or no effect on the levels of cytochrome P450 or on the activities of ethoxyresorufin O-dealkylase and benzyloxy resorufin O-dealkylase in hepatic microsomes [13].
• Furthermore, the increases in the levels of microsomal ethoxyresorufin O-deethylase and erythromycin N-demethylase were accompanied with up-regulation of mdr 1a mRNA in the small intestines of hepatic fibrosis rats when compared to those of the normal rats [14].
• Chemically induced liver cirrhosis in the rat was associated with an increased biosynthesis of the hepatic polyamines putrescine and spermidine and a reduction in the activities of the cytochrome P-450-associated monooxygenase enzymes aryl hydrocarbon hydroxylase, ethoxycoumarin O-deethylase and ethoxyresorufin O-deethylase [15].

Biological context of C13630

• A significant correlation was found between the relative amounts of the immunoreactive protein and benzo(a)-pyrene hydroxylation and 7-ethoxyresorufin O-deethylation activities [16].
• Benzo(a)pyrene hydroxylase, ethoxyresorufin O-deethylase, and methoxycoumarin O-demethylase activities were approximately 15-40% lower in the diploid hepatocyte fraction than in the polyploid cell fraction [17].
• In active smokers the lack of methylation in the studied region of CYP1A1 promoter was associated with a slightly higher pulmonary 7-ethoxyresorufin O-deethylase activity in the regression models allowing for the daily tobacco consumption and age [18].
• The in vitro oxidation of 7-ethoxyresorufin was studied in placental microsomes from 47 full-term pregnancies [19].
• Exposure to green tea gave rise to increases in the O-demethylation of methoxyresorufin and, to a lesser extent, in the dealkylations of ethoxyresorufin and pentoxyresorufin [20].

Anatomical context of C13630

• CYP1A1 messenger RNA (mRNA) and ethoxyresorufin activity were present constitutively in the duodenum of each volunteer [7].
• In hepatic microsomes from methylcholanthrene-treated chicks and rats, MeIQ was a competitive inhibitor of both ethoxyresorufin deethylase activity, a reaction catalyzed mainly by rodent cytochrome P450 IA1, and uroporphyrinogen oxidation, a reaction catalyzed by rodent P450 IA2 [21].
• The induction of ethoxyresorufin O-deethylase in the T47-D cells was the most sensitive aryl hydrocarbon (Ah) receptor-mediated response in both cell lines and this enzyme activity was more inducible than aryl hydrocarbon hydroxylase [22].
• Ethoxyresorufin O-deethylase activity was low to nondetectable in noninduced, mitogen-activated cells, but it was readily detected in 3-methylcholanthrene, mitogen-activated lymphocytes [23].
• The basal activity of 7-ethoxyresorufin O-deethylation of the mucosa of the ethmoturbinates of the rat was comparable to the corresponding activity of the liver [24].

Associations of C13630 with other chemical compounds

• Inhibition by OPZ of AFB1 metabolism by reducing CYP1A2 and CYP3A4 was also demonstrated by decreased activity of their monooxygenase activities toward ethoxyresorufin and nifedipine, respectively [25].
• Anti-P-450 reductase immunoglobulin G inhibited reduced nicotinamide adenine dinucleotide phosphate:cytochrome c reductase activity in prostatic microsomes, and anti-P-450 BNF-B2 but not anti-P-450 PB-B2 immunoglobulin G inhibited the BNF-induced prostatic microsomal 7-ethoxyresorufin O-deethylase and aryl hydrocarbon hydroxylase activities [26].
• The TA1538/ARO strain was proven to express the enzymes, as indicated by high activities of 7-ethoxyresorufin O-deethylase and isoniazid N-acetylase [27].
• AHH, 7-ethoxycoumarin O-deethylase (ECOD), and 7-ethoxyresorufin O-deethylase (EROD) have been used most frequently as substrates to characterize intestinal P450s [28].
• Serial measurements of albumin secretion, urea synthesis, deethylation of ethoxyresorufin (CYT P450 activity), and responsiveness to stimulation with interleukin-6 (IL-6) were performed [29].

Gene context of C13630

• Treatment with 50 microM beta-naphthoflavone resulted in increases in CYP1A2 mRNA (15-fold) and activity (7-ethoxyresorufin O-dealkylation, 27-fold) [30].
• The activities of testosterone 15 alpha-hydroxylase and the Cyp1a-1-mediated 7-ethoxyresorufin O-deethylase (EROD) were decreased in response to cerium [31].
• The possibility that CYP3A4 metabolizes 7-ethoxyresorufin was excluded because there was no correlation between intestinal CYP3A4 catalytic and EROD activity, and cDNA-expressed human CYP3A4 exhibited no EROD activity [32].
• The 17 X 8-hydroxylase activities significantly associated with coumarin 7-hydroxylase activities (r=0.67, p<0.01) in liver microsomes from 17 individuals, but not with ethoxyresorufin O-deethylase activities [33].
• However, a decreased Cyp1a1 activity, as measured by O-deethylation of ethoxyresorufin was observed in lung from TDI-sensitized and challenged mice, suggesting that TDI may inhibit Cyp1a1 function [34].

Analytical, diagnostic and therapeutic context of C13630

• Since in hepatic and pulmonary tissue of model animal systems ethoxyresorufin is a specific substrate for cytochrome P-448-associated monooxygenases, the use of this chemical could proffer an assay that specifically measures human cytochrome P-448-associated activity [23].
• O-Deethylation of 7-ethoxyresorufin was neither sex differentiated nor affected by castration [35].
• Here, we report on the localization of CYP1A1 in the cytosol of kidney and brain, as revealed by immunoblotting with anti-CYP1A1 antibodies and by 7-ethoxyresorufin deethylation (EROD) [36].
• Western blotting together with assays for 7-ethoxyresorufin O-deethylase and methoxyresorufin O-demethylase established that I3C preferentially induced cytochrome P4501A1 over 1A2, consistent with the altered profile of urinary metabolites [37].
• Induction of cytochrome P450 1A1-catalyzed 7-ethoxyresorufin O-deethylase (EROD) activity in mammalian cell culture (EROD bioassay) is thought to be a selective and sensitive parameter used for the quantification of dioxinlike compounds [38].

References