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Adnan A. Elfarra - One of the best experts on this subject based on the ideXlab platform.
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Oxidation of Butadiene Monoxide tomeso-and (±)-Diepoxybutane by cDNA-Expressed Human Cytochrome P450s and by Mouse, Rat, and Human Liver Microsomes: Evidence for Preferential Hydration ofmeso-Diepoxybutane in Rat and Human Liver Microsomes☆
Archives of biochemistry and biophysics, 1997Co-Authors: Renee J. Krause, Adnan A. ElfarraAbstract:Abstract Butadiene monoxide (BM) can be oxidized by cDNA-expressed human cytochrome P450 enzymes and by mouse, rat, and human Liver Microsomes to yield meso - and (±)-diepoxybutane (DEB). The DEB diastereomers were separated by gas chromatography (GC) and characterized by GC–mass spectrometry. Of eight cDNA-expressed human P450 enzymes examined, only incubations with 2E1, 2A6, and 2C9 led to DEB detection; total DEB formation rate by 2E1 was nearly four- and sixfold higher than the rates observed with 2C9 and 2A6, respectively, while incubations with 1A1, 1A2, 2B6, 2D6, or 3A4 did not lead to DEB detection. meso -DEB was detected preferentially in 2A6 and 2E1 incubations (ratios nearly 2:1), whereas incubations with 2C9 led to detection of both isomers in approximately equal amounts. Incubations of mouse, rat, or human Liver Microsomes with BM and chlorzoxazone provided further evidence for the involvement of 2E1 in BM oxidation; meso -DEB was the major DEB form detected at high BM concentrations. The V max / K m ratio for total DEB formation obtained with mouse Liver Microsomes was higher than the ratios obtained with rat and human Liver Microsomes. However, DEB hydrolysis in human Liver Microsomes was greater than that observed with rat Liver Microsomes, while no hydrolysis was detectable in mouse Liver Microsomes. When the DEB diastereomers were added in a 1:1 ratio to human or rat Liver Microsomes, selective hydrolysis of meso -DEB was observed. These results, which characterize new metabolic reactions for BM and DEB, may be of toxicological importance, as significant species differences reflecting both the stereoselective oxidation of BM by P450 enzymes and the subsequent preferential meso -DEB hydration by epoxide hydrolase have been demonstrated.
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oxidation of butadiene monoxide tomeso and diepoxybutane by cdna expressed human cytochrome p450s and by mouse rat and human Liver Microsomes evidence for preferential hydration ofmeso diepoxybutane in rat and human Liver Microsomes
Archives of Biochemistry and Biophysics, 1997Co-Authors: Renee J. Krause, Adnan A. ElfarraAbstract:Abstract Butadiene monoxide (BM) can be oxidized by cDNA-expressed human cytochrome P450 enzymes and by mouse, rat, and human Liver Microsomes to yield meso - and (±)-diepoxybutane (DEB). The DEB diastereomers were separated by gas chromatography (GC) and characterized by GC–mass spectrometry. Of eight cDNA-expressed human P450 enzymes examined, only incubations with 2E1, 2A6, and 2C9 led to DEB detection; total DEB formation rate by 2E1 was nearly four- and sixfold higher than the rates observed with 2C9 and 2A6, respectively, while incubations with 1A1, 1A2, 2B6, 2D6, or 3A4 did not lead to DEB detection. meso -DEB was detected preferentially in 2A6 and 2E1 incubations (ratios nearly 2:1), whereas incubations with 2C9 led to detection of both isomers in approximately equal amounts. Incubations of mouse, rat, or human Liver Microsomes with BM and chlorzoxazone provided further evidence for the involvement of 2E1 in BM oxidation; meso -DEB was the major DEB form detected at high BM concentrations. The V max / K m ratio for total DEB formation obtained with mouse Liver Microsomes was higher than the ratios obtained with rat and human Liver Microsomes. However, DEB hydrolysis in human Liver Microsomes was greater than that observed with rat Liver Microsomes, while no hydrolysis was detectable in mouse Liver Microsomes. When the DEB diastereomers were added in a 1:1 ratio to human or rat Liver Microsomes, selective hydrolysis of meso -DEB was observed. These results, which characterize new metabolic reactions for BM and DEB, may be of toxicological importance, as significant species differences reflecting both the stereoselective oxidation of BM by P450 enzymes and the subsequent preferential meso -DEB hydration by epoxide hydrolase have been demonstrated.
Harish C. Sikka - One of the best experts on this subject based on the ideXlab platform.
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Metabolism of phenanthrene by brown bullhead Liver Microsomes.
Aquatic toxicology (Amsterdam Netherlands), 2003Co-Authors: Jyotsna Pangrekar, Panna L. Kole, Sangeet A. Honey, Subodh Kumar, Harish C. SikkaAbstract:We have investigated the regio- and stereoselective metabolism of phenanthrene by the Liver Microsomes of brown bullhead (Ameriurus nebulosus), a bottom dwelling fish species. The Liver Microsomes from untreated and 3-methylcholanthrene (3-MC)-treated brown bullheads metabolized phenanthrene at a rate of 14.1 and 20.7 pmol/mg protein/min, respectively, indicating that the hydrocarbon is a rather poor substrate for bullhead Liver Microsomes contrary to what has been reported for rat Liver Microsomes. The major phenanthrene metabolites formed by Liver Microsomes from untreated and 3-MC-treated bullheads included benzo-ring 1,2-dihydrodiol (25.3 and 11.6%), K-region 9,10-dihydrodiol (9.6 and 9.6%), and phenols (40.5 and 54.5%). The 3,4-dihydrodiol represented a minor proportion of the total phenanthrene metabolites. The low proportion of the 9,10-dihydrodiol formed by both control and 3-MC-treated bullhead Microsomes sharply contrasts the previous data reported for the corresponding rat Liver Microsomes which metabolized phenanthrene predominantly to its 9,10-dihydrodiol representing 76.6 and 67.1%, respectively of the total metabolites. Liver Microsomes from 3-MC-treated bullheads, like rat Liver Microsomes, were more selective in their attack at the 1,2-position of the benzo-ring than at the 3,4-position of the benzo-ring. Phenanthrene 1,2-dihydrodiol and 3,4-dihydrodiol formed by Liver Microsomes from both control and 3-MC-treated bullheads consisted predominantly of their R,R enantiomer. Phenanthrene, compared with benzo[a]pyrene and chrysene, is metabolized by bullhead Liver microsomal enzymes to its benzo-ring dihydrodiols with a relatively low degree of stereoselectivity.
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Comparative metabolism of chrysene and 5-methylchrysene by rat and rainbow trout Liver Microsomes.
Toxicological sciences : an official journal of the Society of Toxicology, 2003Co-Authors: Nancy W. Shappell, Subodh Kumar, Uli Carlino-macdonald, Shantu Amin, Harish C. SikkaAbstract:We have investigated the metabolism of chrysene (CHR) and 5-methychyrsene (5-MeCHR) by Shasta rainbow trout (Oncorhyncus mykiss) and Long Evans rat Liver Microsomes to assess the effect of a non-benzo ring methyl substituent on the reactions involved in the metabolism of polycyclic aromatic hydrocarbons (PAHs). Trout as well as rat Liver Microsomes metabolized both CHR and 5-MeCHR at essentially similar rates, indicating that the methyl substituent does not alter the substrate specificity of the cytochrome P450(s) involved in the metabolism of the two PAHs. Dihydrodiols were the major CHR metabolites formed by both trout and rat Liver Microsomes, whereas the trout Liver Microsomes formed a considerably higher proportion of 5-MeCHR phenols compared to diols, indicating that 5-methyl substitution alters the substrate specificity of trout microsomal epoxide hydrolase for 5-MeCHR epoxides. Unlike trout Liver Microsomes, rat Liver Microsomes formed a much greater proportion of 5-MeCHR diols compared to 5-MeCHR phenols, suggesting that 5-MeCHR epoxides are better substrates for the microsomal epoxide hydrolase present in rat Liver than for the enzyme in trout Liver. Both trout and rat Liver Microsomes are more efficient at attacking the bay-region bond versus the non-bay-region double bond in chrysene. In contrast the reverse is true in the case of 5-MeCHR, indicating that a non-benzo ring methyl substituent alters the regioselectivity of the enzymes involved in the oxidative metabolism of PAHs.
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Metabolism of chrysene by brown bullhead Liver Microsomes.
Toxicological sciences : an official journal of the Society of Toxicology, 2003Co-Authors: Jyotsna Pangrekar, Panna L. Kole, Sangeet A. Honey, Subodh Kumar, Harish C. SikkaAbstract:We have investigated the regio- and stereoselective metabolism of chrysene, a four-ring symmetrical carcinogenic polycyclic aromatic hydrocarbon (PAH), by the Liver Microsomes of brown bullhead (Ameriurus nebulosus), a bottom-dwelling fish species. The Liver Microsomes from untreated and 3-methylcholanthrene (3-MC)-treated brown bullheads metabolized chrysene at the rate of 30.1 and 82.2 pmol/mg protein/min, respectively. Benzo-ring diols (1,2-diol and 3,4-diol) were the major chrysene metabolites formed by Liver Microsomes from control and 3-MC-treated fish. However, the control Microsomes produced a considerably higher proportion of chrysene 1,2-diol (benzo-ring diol with a bay region double bond) plus 1-hydroxychrysene, than 3,4-diol plus 3-hydroxychrysene, indicating that these Microsomes are selective in attacking the 1,2- position of the benzo-ring. On the other hand, 3-MC-induced Microsomes did not show such a regioselectivity in the metabolism of chrysene. Control bullhead Liver Microsomes, compared to control rat Liver Microsomes, produced a considerably higher proportion of chrysene 1,2-diol, the putative proximate carcinogenic metabolite of chrysene. Like rat Liver Microsomes, bullhead Liver Microsomes produced only trace amounts of the K-region diol. Chrysene 1,2-diol and 3,4-diol formed by the Liver micrsomes from both control and 3-MC-treated bullheads consisted predominantly of their R,R-enantiomers. Chrysene is metabolized by bullhead Liver microsomal enzymes to its benzo-ring diols with a relatively lower degree of stereoselectivity compared to benzo[a]pyrene (a five-ring PAH), but with a higher degree of stereoselectivity compared to phenanthrene (a three-ring PAH). The data of this study, together with those from our previous studies with phenanthrene, benzo[a]pyrene and dibenzo[a,l]pyrene (a six-ring PAH), indicate that the regioselectivity in
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Metabolism of benzo(a)pyrene by duck Liver Microsomes
Comparative biochemistry and physiology. Toxicology & pharmacology : CBP, 2000Co-Authors: Sangeet A. Honey, Subodh Kumar, Patrick O’keefe, Adam T. Drahushuk, James R. Olson, Harish C. SikkaAbstract:Abstract The metabolism of benzo(a)pyrene [BP], a model carcinogenic PAH, by hepatic Microsomes of two duck species, mallard (Anas platyrhynchos) and common merganser (Mergus merganser americanus) collected from chemically-contaminated and relatively non-contaminated areas was investigated. The rate of metabolism of BP by Liver Microsomes of common merganser and mallard collected from polluted areas (2650±310 and 2200±310 pmol/min per mg microsomal protein, respectively) was significantly higher than that obtained with Liver Microsomes of the two species collected from non-polluted areas (334±33 and 231±30 pmol/min per mg microsomal protein, respectively). The level of cytochrome P-450 1A1 was significantly higher in the Liver Microsomes of both duck species from the polluted areas as compared to the ducks from the non-polluted areas. The major BP metabolites, including BP-9, 10-diol, BP-4, 5-diol, BP-7, 8-diol, BP-1, 6-dione, BP-3, 6-dione, BP-6, 12-dione, 9-hydroxy-BP and 3-hydroxy-BP, formed by Liver Microsomes of both duck species from polluted and non-polluted areas, were qualitatively similar. However, the patterns of these metabolites were considerably different from each other. Liver Microsomes of ducks from the polluted areas produced a higher proportion of benzo-ring dihydrodiols than the Liver Microsomes of ducks from the non-polluted areas, which converted a greater proportion of BP to BP-phenols. The predominant enantiomer of BP-7,8-diol formed by hepatic Microsomes of the two duck species had an (−)R,R absolute stereochemistry. The data suggest that duck and rat Liver microsomal enzymes have different regioselectivity but similar stereoselectivity in the metabolism of BP.
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Comparative metabolism of benzo[a]pyrene by Liver Microsomes of channel catfish and brown bullhead
Environmental Toxicology and Chemistry, 1997Co-Authors: Zhi-xin Yuan, Subodh Kumar, Harish C. SikkaAbstract:We investigated the metabolism of the carcinogen benzo[a]pyrene (BaP) by Liver Microsomes of channel catfish (Ictalurus punctatus) and brown bullhead (Ameiurus nebulosus) pretreated with 3-methylcholanthrene. The catfish Liver Microsomes metabolized BaP at a considerably lower rate than did the brown bullhead Liver Microsomes. Although the BaP metabolites produced by the Liver Microsomes of the two species were qualitatively similiar, there were considerable differences in the relative proportions of individual metabolites formed. The catfish Liver Microsomes produced a considerably lower proportion of benzo-ring diols of BaP including BaP-7,8-diol (the proximate carcinogenic metabolite of BaP) than did the bullhead Liver Microsomes. Compared to the bullhead Liver Microsomes, the catfish Microsomes converted a higher proportion of BaP to phenolic metabolites.
Renee J. Krause - One of the best experts on this subject based on the ideXlab platform.
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Oxidation of Butadiene Monoxide tomeso-and (±)-Diepoxybutane by cDNA-Expressed Human Cytochrome P450s and by Mouse, Rat, and Human Liver Microsomes: Evidence for Preferential Hydration ofmeso-Diepoxybutane in Rat and Human Liver Microsomes☆
Archives of biochemistry and biophysics, 1997Co-Authors: Renee J. Krause, Adnan A. ElfarraAbstract:Abstract Butadiene monoxide (BM) can be oxidized by cDNA-expressed human cytochrome P450 enzymes and by mouse, rat, and human Liver Microsomes to yield meso - and (±)-diepoxybutane (DEB). The DEB diastereomers were separated by gas chromatography (GC) and characterized by GC–mass spectrometry. Of eight cDNA-expressed human P450 enzymes examined, only incubations with 2E1, 2A6, and 2C9 led to DEB detection; total DEB formation rate by 2E1 was nearly four- and sixfold higher than the rates observed with 2C9 and 2A6, respectively, while incubations with 1A1, 1A2, 2B6, 2D6, or 3A4 did not lead to DEB detection. meso -DEB was detected preferentially in 2A6 and 2E1 incubations (ratios nearly 2:1), whereas incubations with 2C9 led to detection of both isomers in approximately equal amounts. Incubations of mouse, rat, or human Liver Microsomes with BM and chlorzoxazone provided further evidence for the involvement of 2E1 in BM oxidation; meso -DEB was the major DEB form detected at high BM concentrations. The V max / K m ratio for total DEB formation obtained with mouse Liver Microsomes was higher than the ratios obtained with rat and human Liver Microsomes. However, DEB hydrolysis in human Liver Microsomes was greater than that observed with rat Liver Microsomes, while no hydrolysis was detectable in mouse Liver Microsomes. When the DEB diastereomers were added in a 1:1 ratio to human or rat Liver Microsomes, selective hydrolysis of meso -DEB was observed. These results, which characterize new metabolic reactions for BM and DEB, may be of toxicological importance, as significant species differences reflecting both the stereoselective oxidation of BM by P450 enzymes and the subsequent preferential meso -DEB hydration by epoxide hydrolase have been demonstrated.
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oxidation of butadiene monoxide tomeso and diepoxybutane by cdna expressed human cytochrome p450s and by mouse rat and human Liver Microsomes evidence for preferential hydration ofmeso diepoxybutane in rat and human Liver Microsomes
Archives of Biochemistry and Biophysics, 1997Co-Authors: Renee J. Krause, Adnan A. ElfarraAbstract:Abstract Butadiene monoxide (BM) can be oxidized by cDNA-expressed human cytochrome P450 enzymes and by mouse, rat, and human Liver Microsomes to yield meso - and (±)-diepoxybutane (DEB). The DEB diastereomers were separated by gas chromatography (GC) and characterized by GC–mass spectrometry. Of eight cDNA-expressed human P450 enzymes examined, only incubations with 2E1, 2A6, and 2C9 led to DEB detection; total DEB formation rate by 2E1 was nearly four- and sixfold higher than the rates observed with 2C9 and 2A6, respectively, while incubations with 1A1, 1A2, 2B6, 2D6, or 3A4 did not lead to DEB detection. meso -DEB was detected preferentially in 2A6 and 2E1 incubations (ratios nearly 2:1), whereas incubations with 2C9 led to detection of both isomers in approximately equal amounts. Incubations of mouse, rat, or human Liver Microsomes with BM and chlorzoxazone provided further evidence for the involvement of 2E1 in BM oxidation; meso -DEB was the major DEB form detected at high BM concentrations. The V max / K m ratio for total DEB formation obtained with mouse Liver Microsomes was higher than the ratios obtained with rat and human Liver Microsomes. However, DEB hydrolysis in human Liver Microsomes was greater than that observed with rat Liver Microsomes, while no hydrolysis was detectable in mouse Liver Microsomes. When the DEB diastereomers were added in a 1:1 ratio to human or rat Liver Microsomes, selective hydrolysis of meso -DEB was observed. These results, which characterize new metabolic reactions for BM and DEB, may be of toxicological importance, as significant species differences reflecting both the stereoselective oxidation of BM by P450 enzymes and the subsequent preferential meso -DEB hydration by epoxide hydrolase have been demonstrated.
Drew Fackett - One of the best experts on this subject based on the ideXlab platform.
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a comparison of aroclor 1254 induced and uninduced rat Liver Microsomes to human Liver Microsomes in phenytoin o deethylation coumarin 7 hydroxylation tolbutamide 4 hydroxylation s mephenytoin 4 hydroxylation chloroxazone 6 hydroxylation and testoste
Chemico-Biological Interactions, 2001Co-Authors: Judy Easterbrook, Drew Fackett, Albert P LiAbstract:Abstract Aroclor 1254-induced rat Liver homogenate supernatant (Liver S-9) is routinely used as an exogenous metabolic activation system for the evaluation of mutagenicity of xenobiotics. The purpose of this study is to evaluate whether results obtained with Aroclor 1254-induced Liver Microsomes would be relevant to human. Aroclor 1254-induced and uninduced rat Liver Microsomes were compared to human Liver Microsomes in the metabolism of substrates which are known to be selectively metabolized by the major human cytochrome P450 (CYP) isoforms. The activities studied and the major CYP isoforms involved were as follows: phenacetin O -deethylation (CYP1A2); coumarin 7-hydroxylation, (CYP2A6); tolbutamide 4-hydroxylation (CYP2C9), S- mephenytoin 4′-hydroxylation (CYP2C19); dextromethorphan O -demethylation (CYP2D6); chloroxazone 6-hydroxylation (CYP2E1); and testosterone 6β-hydroxylation (CYP3A4). We found that both induced and uninduced rat Liver Microsomes were active in all the pathways studied with the exception of coumarin 7-hydroxylation. Coumarin 7-hydroxylation was observed with human Liver Microsomes but not the rat Liver Microsomes. Aroclor-1254 was found to induce all activities measured, with the exception of coumarin 7-hydroxylation. Dextromethorphan O -deethylation activity was higher in the rat Liver Microsomes than the human Liver Microsomes. Testosterone 6β-hydroxylation activity was found to be similar between the human Liver Microsomes and the induced rat Liver Microsomes. Our results suggest that experimental data obtained with Aroclor 1254-induced rat Liver Microsomes may not always be relevant to human.
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a comparison of aroclor 1254 induced and uninduced rat Liver Microsomes to human Liver Microsomes in phenytoin o deethylation coumarin 7 hydroxylation tolbutamide 4 hydroxylation s mephenytoin 4 hydroxylation chloroxazone 6 hydroxylation and testoste
Chemico-Biological Interactions, 2001Co-Authors: Judy Easterbrook, Drew FackettAbstract:Aroclor 1254-induced rat Liver homogenate supernatant (Liver S-9) is routinely used as an exogenous metabolic activation system for the evaluation of mutagenicity of xenobiotics. The purpose of this study is to evaluate whether results obtained with Aroclor 1254-induced Liver Microsomes would be relevant to human. Aroclor 1254-induced and uninduced rat Liver Microsomes were compared to human Liver Microsomes in the metabolism of substrates which are known to be selectively metabolized by the major human cytochrome P450 (CYP) isoforms. The activities studied and the major CYP isoforms involved were as follows: phenacetin O-deethylation (CYP1A2); coumarin 7-hydroxylation, (CYP2A6); tolbutamide 4-hydroxylation (CYP2C9), S-mephenytoin 4'-hydroxylation (CYP2C19); dextromethorphan O-demethylation (CYP2D6); chloroxazone 6-hydroxylation (CYP2E1); and testosterone 6beta-hydroxylation (CYP3A4). We found that both induced and uninduced rat Liver Microsomes were active in all the pathways studied with the exception of coumarin 7-hydroxylation. Coumarin 7-hydroxylation was observed with human Liver Microsomes but not the rat Liver Microsomes. Aroclor-1254 was found to induce all activities measured, with the exception of coumarin 7-hydroxylation. Dextromethorphan O-deethylation activity was higher in the rat Liver Microsomes than the human Liver Microsomes. Testosterone 6beta-hydroxylation activity was found to be similar between the human Liver Microsomes and the induced rat Liver Microsomes. Our results suggest that experimental data obtained with Aroclor 1254-induced rat Liver Microsomes may not always be relevant to human.
Judy Easterbrook - One of the best experts on this subject based on the ideXlab platform.
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a comparison of aroclor 1254 induced and uninduced rat Liver Microsomes to human Liver Microsomes in phenytoin o deethylation coumarin 7 hydroxylation tolbutamide 4 hydroxylation s mephenytoin 4 hydroxylation chloroxazone 6 hydroxylation and testoste
Chemico-Biological Interactions, 2001Co-Authors: Judy Easterbrook, Drew Fackett, Albert P LiAbstract:Abstract Aroclor 1254-induced rat Liver homogenate supernatant (Liver S-9) is routinely used as an exogenous metabolic activation system for the evaluation of mutagenicity of xenobiotics. The purpose of this study is to evaluate whether results obtained with Aroclor 1254-induced Liver Microsomes would be relevant to human. Aroclor 1254-induced and uninduced rat Liver Microsomes were compared to human Liver Microsomes in the metabolism of substrates which are known to be selectively metabolized by the major human cytochrome P450 (CYP) isoforms. The activities studied and the major CYP isoforms involved were as follows: phenacetin O -deethylation (CYP1A2); coumarin 7-hydroxylation, (CYP2A6); tolbutamide 4-hydroxylation (CYP2C9), S- mephenytoin 4′-hydroxylation (CYP2C19); dextromethorphan O -demethylation (CYP2D6); chloroxazone 6-hydroxylation (CYP2E1); and testosterone 6β-hydroxylation (CYP3A4). We found that both induced and uninduced rat Liver Microsomes were active in all the pathways studied with the exception of coumarin 7-hydroxylation. Coumarin 7-hydroxylation was observed with human Liver Microsomes but not the rat Liver Microsomes. Aroclor-1254 was found to induce all activities measured, with the exception of coumarin 7-hydroxylation. Dextromethorphan O -deethylation activity was higher in the rat Liver Microsomes than the human Liver Microsomes. Testosterone 6β-hydroxylation activity was found to be similar between the human Liver Microsomes and the induced rat Liver Microsomes. Our results suggest that experimental data obtained with Aroclor 1254-induced rat Liver Microsomes may not always be relevant to human.
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a comparison of aroclor 1254 induced and uninduced rat Liver Microsomes to human Liver Microsomes in phenytoin o deethylation coumarin 7 hydroxylation tolbutamide 4 hydroxylation s mephenytoin 4 hydroxylation chloroxazone 6 hydroxylation and testoste
Chemico-Biological Interactions, 2001Co-Authors: Judy Easterbrook, Drew FackettAbstract:Aroclor 1254-induced rat Liver homogenate supernatant (Liver S-9) is routinely used as an exogenous metabolic activation system for the evaluation of mutagenicity of xenobiotics. The purpose of this study is to evaluate whether results obtained with Aroclor 1254-induced Liver Microsomes would be relevant to human. Aroclor 1254-induced and uninduced rat Liver Microsomes were compared to human Liver Microsomes in the metabolism of substrates which are known to be selectively metabolized by the major human cytochrome P450 (CYP) isoforms. The activities studied and the major CYP isoforms involved were as follows: phenacetin O-deethylation (CYP1A2); coumarin 7-hydroxylation, (CYP2A6); tolbutamide 4-hydroxylation (CYP2C9), S-mephenytoin 4'-hydroxylation (CYP2C19); dextromethorphan O-demethylation (CYP2D6); chloroxazone 6-hydroxylation (CYP2E1); and testosterone 6beta-hydroxylation (CYP3A4). We found that both induced and uninduced rat Liver Microsomes were active in all the pathways studied with the exception of coumarin 7-hydroxylation. Coumarin 7-hydroxylation was observed with human Liver Microsomes but not the rat Liver Microsomes. Aroclor-1254 was found to induce all activities measured, with the exception of coumarin 7-hydroxylation. Dextromethorphan O-deethylation activity was higher in the rat Liver Microsomes than the human Liver Microsomes. Testosterone 6beta-hydroxylation activity was found to be similar between the human Liver Microsomes and the induced rat Liver Microsomes. Our results suggest that experimental data obtained with Aroclor 1254-induced rat Liver Microsomes may not always be relevant to human.
