The Experts below are selected from a list of 114867 Experts worldwide ranked by ideXlab platform
Tetsuya Kamataki - One of the best experts on this subject based on the ideXlab platform.
-
a high level expression of cyp2A in the lung of the suncus suncus murinus and its role in the activation of 4 methylnitrosamino 1 3 pyridyl 1 butanone
Biochemical and Biophysical Research Communications, 2000Co-Authors: Taisei Mushiroda, Noritaka Ariyoshi, Kanzo Kimura, Eiji Takahara, Osamu Nagata, Hideo Kato, Tetsuya KamatakiAbstract:Abstract Northern blot analysis of mRNA prepared from the lung of Suncus murinus (suncus), which was classified as an ancestor of primates, revealed that the expression level of Cytochrome P450 2A (CYP2A) mRNA was about 100-fold higher than in the lung from rats and mice. To confirm that the pulmonary CYP2A of the suncus had a catalytic activity, the metabolism of a specific substrate for CYP2A6, (+)-cis-3,5-dimethyl-2-(3-pyridyl) thiazolidin-4-one hydrochloride (SM-12502), was determined. The intrinsic clearance for SM-12502 S-oxidation by the suncus lung microsomes was calculated to be 99-fold higher than that by rat liver microsomes. The mutagen-producing activity of a 9000g supernatant fraction prepared from suncus lung was examined using 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) as a promutagen. The results showed that the suncus lung possessed 82-fold higher mutagen-producing activity than the rat lung, indicating that NNK was efficiently activated by the CYP2A isoform expressed in the suncus lung and that the suncus was a sensitive animal species to the genotoxicity of NNK contained in tobacco smoke.
Alan R Dahl - One of the best experts on this subject based on the ideXlab platform.
-
nasal Cytochrome P450 2A identification regional localization and metabolic activity toward hexamethylphosphoramide a known nasal carcinogen
Toxicology and Applied Pharmacology, 1997Co-Authors: Janice R Thorntonmanning, Kristen J Nikula, Jon A Hotchkiss, Kelly J Avila, Kevin D Rohrbacher, Alan R DahlAbstract:Abstract Two members of the Cytochrome P450 2A subfamily, CYP2A10 and 2A11, are abundant nasal enzymes previously characterized in rabbit olfactory microsomes. Rabbit CYP2A is active toward a number of nasal toxicants, including the rat nasal procarcinogen hexamethylphosphoramide (HMPA). While P450s immunochemically related to the rabbit CYP2As have been detected in rat and human nasal mucosa, confirmation of these enzymes as members of the CYP2A subfamily and efforts to characterize their ability to bioactivate toxicants have been limited. In the present study, the regional distribution and cell-specific expression of CYP2A in the rat nasal cavity were examined using an antibody to rabbit CYP2A10/11. In sections of the anterior nose, immunoreactive CYP2A was present in ciliated cells of the nasal respiratory epithelium and cuboidal epithelial cells of the nasal transitional epithelium, but was absent in squamous epithelial cells. The most intense immunostaining was observed in the posterior nose. Olfactory sustentacular cells and Bowman's gland cells in sections posterior to the nasal papilla stained most intensely. Western blot analysis revealed that anti-CYP2A10/11 recognized a sharp band of approximately 50 kDa in nasal respiratory and olfactory microsomes, supporting the premise that the antibody is reacting with a Cytochrome P450 enzyme. The nasal expression of CYP2A6 mRNA—a member of the human CYP2A subfamily having a high degree of homology to rabbit 2A10 and 2A11—was examined in human surgical patients. Middle turbinectomy tissues—largely composed of nasal respiratory epithelia—from 11 patients were analyzed for the presence of CYP2A6 using reverse transcription–polymerase chain reaction (RT–PCR). Identification of CYP2A6 was confirmed by DNA sequencing of RT–PCR products. CYP2A6 mRNA was detected in all of the human samples analyzed. In additional experiments, human CYP2A6 metabolized HMPA to formaldehyde, suggesting that this compound might cause nasal toxicity in humans. The identification of CYP2A Cytochromes in rat and human nasal tissues may have important implications for risk assessment of inhaled xenobiotics.
Taisei Mushiroda - One of the best experts on this subject based on the ideXlab platform.
-
a high level expression of cyp2A in the lung of the suncus suncus murinus and its role in the activation of 4 methylnitrosamino 1 3 pyridyl 1 butanone
Biochemical and Biophysical Research Communications, 2000Co-Authors: Taisei Mushiroda, Noritaka Ariyoshi, Kanzo Kimura, Eiji Takahara, Osamu Nagata, Hideo Kato, Tetsuya KamatakiAbstract:Abstract Northern blot analysis of mRNA prepared from the lung of Suncus murinus (suncus), which was classified as an ancestor of primates, revealed that the expression level of Cytochrome P450 2A (CYP2A) mRNA was about 100-fold higher than in the lung from rats and mice. To confirm that the pulmonary CYP2A of the suncus had a catalytic activity, the metabolism of a specific substrate for CYP2A6, (+)-cis-3,5-dimethyl-2-(3-pyridyl) thiazolidin-4-one hydrochloride (SM-12502), was determined. The intrinsic clearance for SM-12502 S-oxidation by the suncus lung microsomes was calculated to be 99-fold higher than that by rat liver microsomes. The mutagen-producing activity of a 9000g supernatant fraction prepared from suncus lung was examined using 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) as a promutagen. The results showed that the suncus lung possessed 82-fold higher mutagen-producing activity than the rat lung, indicating that NNK was efficiently activated by the CYP2A isoform expressed in the suncus lung and that the suncus was a sensitive animal species to the genotoxicity of NNK contained in tobacco smoke.
Janice R Thorntonmanning - One of the best experts on this subject based on the ideXlab platform.
-
nasal Cytochrome P450 2A identification regional localization and metabolic activity toward hexamethylphosphoramide a known nasal carcinogen
Toxicology and Applied Pharmacology, 1997Co-Authors: Janice R Thorntonmanning, Kristen J Nikula, Jon A Hotchkiss, Kelly J Avila, Kevin D Rohrbacher, Alan R DahlAbstract:Abstract Two members of the Cytochrome P450 2A subfamily, CYP2A10 and 2A11, are abundant nasal enzymes previously characterized in rabbit olfactory microsomes. Rabbit CYP2A is active toward a number of nasal toxicants, including the rat nasal procarcinogen hexamethylphosphoramide (HMPA). While P450s immunochemically related to the rabbit CYP2As have been detected in rat and human nasal mucosa, confirmation of these enzymes as members of the CYP2A subfamily and efforts to characterize their ability to bioactivate toxicants have been limited. In the present study, the regional distribution and cell-specific expression of CYP2A in the rat nasal cavity were examined using an antibody to rabbit CYP2A10/11. In sections of the anterior nose, immunoreactive CYP2A was present in ciliated cells of the nasal respiratory epithelium and cuboidal epithelial cells of the nasal transitional epithelium, but was absent in squamous epithelial cells. The most intense immunostaining was observed in the posterior nose. Olfactory sustentacular cells and Bowman's gland cells in sections posterior to the nasal papilla stained most intensely. Western blot analysis revealed that anti-CYP2A10/11 recognized a sharp band of approximately 50 kDa in nasal respiratory and olfactory microsomes, supporting the premise that the antibody is reacting with a Cytochrome P450 enzyme. The nasal expression of CYP2A6 mRNA—a member of the human CYP2A subfamily having a high degree of homology to rabbit 2A10 and 2A11—was examined in human surgical patients. Middle turbinectomy tissues—largely composed of nasal respiratory epithelia—from 11 patients were analyzed for the presence of CYP2A6 using reverse transcription–polymerase chain reaction (RT–PCR). Identification of CYP2A6 was confirmed by DNA sequencing of RT–PCR products. CYP2A6 mRNA was detected in all of the human samples analyzed. In additional experiments, human CYP2A6 metabolized HMPA to formaldehyde, suggesting that this compound might cause nasal toxicity in humans. The identification of CYP2A Cytochromes in rat and human nasal tissues may have important implications for risk assessment of inhaled xenobiotics.
Hideo Kato - One of the best experts on this subject based on the ideXlab platform.
-
a high level expression of cyp2A in the lung of the suncus suncus murinus and its role in the activation of 4 methylnitrosamino 1 3 pyridyl 1 butanone
Biochemical and Biophysical Research Communications, 2000Co-Authors: Taisei Mushiroda, Noritaka Ariyoshi, Kanzo Kimura, Eiji Takahara, Osamu Nagata, Hideo Kato, Tetsuya KamatakiAbstract:Abstract Northern blot analysis of mRNA prepared from the lung of Suncus murinus (suncus), which was classified as an ancestor of primates, revealed that the expression level of Cytochrome P450 2A (CYP2A) mRNA was about 100-fold higher than in the lung from rats and mice. To confirm that the pulmonary CYP2A of the suncus had a catalytic activity, the metabolism of a specific substrate for CYP2A6, (+)-cis-3,5-dimethyl-2-(3-pyridyl) thiazolidin-4-one hydrochloride (SM-12502), was determined. The intrinsic clearance for SM-12502 S-oxidation by the suncus lung microsomes was calculated to be 99-fold higher than that by rat liver microsomes. The mutagen-producing activity of a 9000g supernatant fraction prepared from suncus lung was examined using 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) as a promutagen. The results showed that the suncus lung possessed 82-fold higher mutagen-producing activity than the rat lung, indicating that NNK was efficiently activated by the CYP2A isoform expressed in the suncus lung and that the suncus was a sensitive animal species to the genotoxicity of NNK contained in tobacco smoke.
