Alkoxyresorufin O-dealkylases: Association with the murine Ah locus

Lum, Peck Y.; Burke, Mary; Mayer, Richard T.; Ioannides, Costas

doi:10.1016/0304-3835(86)90177-1

Cited by 12 publications

(3 citation statements)

References 17 publications

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“…For glucosinolates to induce significantly the dealkylation of the two alkoxyresorufins, used as probes for the Ah-regulated CYP1 family, , it was essential for the slices to be in contact with the inducing agent for at least 6 h; the rise in CYP1A1 and CYP1A2 apoprotein levels observed in the pooled slices indicates that increased enzyme availability is at least partly responsible for this effect. Although erucin and R- sulforaphane, the isothiocyanates emanating from glucoerucin and glucoraphanin, respectively, also up-regulate the CYP1 family at the protein level, no increase in activity can be discerned as these compounds are also effective mechanism-based inhibitors, and for this reason, the dealkylation of alkoxyresorufins was not assessed in the current studies following incubation with the isothiocyanates.…”

Section: Discussionmentioning

confidence: 99%

Characterization of the Temporal Induction of Hepatic Xenobiotic-Metabolizing Enzymes by Glucosinolates and Isothiocyanates: Requirement for at Least a 6 h Exposure To Elicit Complete Induction Profile

Razis

Bagatta

Nicola

et al. 2012

J. Agric. Food Chem.

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A mechanism of action of chemopreventive glucosinolates/isothiocyanates, established largely in vitro, is to modulate carcinogen-metabolizing enzymes. Extrapolation in vivo involves relating in vitro concentrations to plasma/tissue concentrations attained in vivo, thus assuming that even transient exposure modulates enzyme activity. To test this hypothesis, precision-cut rat liver slices were incubated with glucosinolates for up to 24 h, and the O-dealkylation of methoxyresorufin and ethoxyresorufin was determined; increased activities were observed only at incubations of at least 6 h. To evaluate phase II enzymes, isothiocyanates, namely, sulforaphane, erucin, and phenethyl isothiocyanate, were similarly incubated; quinone reductase increased after incubation for 6 h or longer. When glutathione S-transferase was monitored, the phenethyl isothiocyanate-manifested rise necessitated at least a 6 h incubation, whereas in the case of sulforaphane and erucin, the activity was elevated after only 2 h. It is inferred that a rise in carcinogen-metabolizing enzymes by glucosinolates/isothiocyanates necessitates tissue exposure of at least 6 h.

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Section: Discussionmentioning

confidence: 99%

Characterization of the Temporal Induction of Hepatic Xenobiotic-Metabolizing Enzymes by Glucosinolates and Isothiocyanates: Requirement for at Least a 6 h Exposure To Elicit Complete Induction Profile

Razis

Bagatta

Nicola

et al. 2012

J. Agric. Food Chem.

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“…(Thomas et al, 1972;Thomas & Hutton, 1973;Robinson et al, 1974;Nebert et al, 1982). Liver microsomal ethoxyphenoxazone de-ethylase (ethoxyresorufin deethylase) is another cytochrome P1-450-mediated hydroxylase activity which is highly induced by 3-methylcholanthrene and ,-naphthoflavone in C57BL/10 mice (Burke & Mayer, 1983;Smith et al, 1986b), but not in the DBA/2 strain (Lum et al, 1986) and correlates with aryl hydrocarbon hydroxylase activity in Heterogeneic Stock mice (Lang et al, 1981). The induction of hepatic ethoxyphenoxazone activity in the 12 mouse strains after a single oral dose of ,f-naphthoflavone was determined and compared with the induction observed with an equivalent dose of HCB (Table 2).…”

Section: Genetic Variationmentioning

confidence: 99%

Chemically-induced formation of an inhibitor of hepatic uroporphyrinogen decarboxylase in inbred mice with iron overload

Smith

Francis

1987

Biochemical Journal

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An inhibitor of hepatic uroporphyrinogen decarboxylase (EC 4.1.1.37) was demonstrated in heat-treated extracts of livers from C57BL/10ScSn mice with iron overload after a single dose (100 mg/kg; 350 mumol/kg) of hexachlorobenzene (HCB). Inhibition was not due to accumulated uroporphyrin since this could be removed by a SEP-PAK C18 cartridge without affecting inhibitor activity. The presence of the inhibitor could be first demonstrated 2 weeks after mice received HCB and before major elevation of hepatic porphyrin levels. Maximum inhibitory potential was reached at about 8 weeks and was still detected 25 weeks after the chemical, thus paralleling the depression of enzyme activity reported previously [Smith, Francis, Kay, Greig & Stewart (1986) Biochem. J. 238, 871-878]. The inhibitor was not detected following treatment of mice with either iron or HCB alone or after the decarboxylase activity was destroyed in vitro by the combination of uroporphyrin and light. The formation of the inhibitor by inbred mouse strains nominally Ah-responsive (C57BL/6J, C57BL/10ScSn, BALB/c, C3H/HeJ, CBA/J and A/J) and Ah-nonresponsive (SWR, AKR, 129, SJL, LP and DBA/2) did not correlate fully with their reported Ah-phenotype. There was a correlation amongst the Ah-responsive strains only, with hepatic ethoxyphenoxazone de-ethylase activity induced in parallel experiments by treatment with beta-naphthoflavone. De-ethylase activity induced by HCB, however, was considerably less than that with beta-naphthoflavone, which has not been reported as porphyrogenic. Other polyhalogenated chemicals, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin, 2,3,4,2',3',4'-hexachlorobiphenyl and hexabromobenzene, also caused the formation of the inhibitor of uroporphyrinogen decarboxylase.

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“…Induction of CYP1A2 is mediated by an AhR‐dependent mechanism and an AhR‐independent mechanism, depending on the nature of the inducer (Ryu et al ., ). Treatment with a typical CYP1A inducer, 3‐methylchloranthrene (3‐MC), enhanced the rate of dealkylation of all alkoxyresorufins in C57BL/6 mice but not in DBA/2 mice, which are AhR‐non‐responsive (Lum et al ., ; Moriguchi et al ., ). As seen in the present study, an AhR agonist, BNF, did not alter EROD or MROD activities in DBA/2 mice (Fig.…”

Section: Discussionmentioning

confidence: 97%

Different profiles of hepatic alkoxyresorufin O‐dealkylase activities in small rodents

Chatuphonprasert

Rermraksakul

Udomsuk

et al. 2012

J of Applied Toxicology

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The aims of the present study were to determine cytochrome P450 enzyme activity in six strains of experimental rodents (n = 5/sex/species): ICR, C57BL/6 and DBA/2 mice; Sprague Dawley and Wistar rats; and Dunkin Hartley guinea pigs. After animals were treated with the typical inducers β-naphthoflavone (BNF), dexamethasone (DEX) and phenobarbital (PB), the levels of O-dealkylation of ethoxyresorufin (EROD), methoxyresorufin (MROD), pentoxyresorufin (PROD) and benzyloxyresorufin (BROD) activity were determined using responsive catalytic reactions to study CYP1A1, CYP1A2 and CYP2B, respectively. A maximal induction of EROD and MROD was found in BNF-treated animals from all strains (2.4- to 15.1-fold) except DBA/2 (0.9- to 1.8-fold). C57BL/6 mice had the strongest BNF-induced EROD (15.1-fold) and MROD (8.3-fold) activities. No differences in BNF-induced EROD and MROD activities were observed between males and females. However, the EROD activity of Wistar rats and the MROD activity of Sprague Dawley rats were higher in males than females. DEX induced PROD activity only in mice (1.3- to 7.1-fold), but not in rats and guinea pigs (0.2- to 1.1-fold). However, induction of BROD activity was found in DEX-treated mice and rats (1.5 to 12.5-fold), but not in guinea pigs (0.3 to 0.4-fold). PB caused a significant elevation of PROD (1.7- to 10.4-fold) and BROD (31- to 13.2-fold) activities in all the animals. PB-induced BROD activity was higher in females than males in Sprague Dawley rats. These observations strongly suggest that the choice of experimental animal strain, species and inducer is of critical importance for studies of drug metabolism and interaction.

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Alkoxyresorufin O-dealkylases: Association with the murine Ah locus

Cited by 12 publications

References 17 publications

Characterization of the Temporal Induction of Hepatic Xenobiotic-Metabolizing Enzymes by Glucosinolates and Isothiocyanates: Requirement for at Least a 6 h Exposure To Elicit Complete Induction Profile

Characterization of the Temporal Induction of Hepatic Xenobiotic-Metabolizing Enzymes by Glucosinolates and Isothiocyanates: Requirement for at Least a 6 h Exposure To Elicit Complete Induction Profile

Chemically-induced formation of an inhibitor of hepatic uroporphyrinogen decarboxylase in inbred mice with iron overload

Different profiles of hepatic alkoxyresorufin O‐dealkylase activities in small rodents

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