000			02192nam a2200217Ia 4500
003			MX-MdCICY
005			20250625162418.0
040			_cCICY
090			_aB-18748
245	1	0	_aIdentification of the Main Human Cytochrome P450 Enzymes Involved in Safrole 1'-Hydroxylation
490	0		_vChem. Res. Toxicol., p.1151-1156, 2004
520	3		_aSafrole is a natural plant constituent, found in sassafras oil and certain other essential oils. The carcinogenicity of safrole is mediated through 1'-hydroxysafrole formation, followed by sulfonation to an unstable sulfate that reacts to form DNA adducts. To identify the main cytochrome P450 (P450)involved in human hepatic safrole 1'-hydroxylation (SOH), we determined the SOH activities of human liver microsomes andEscherichia colimembranes expressing bicistronic human P450s. Human liver (n)18)microsomal SOH activities were in the range of 3.5-16.9 nmol/min/mg protein with a mean value of 8.7(0.7 nmol/min/mg protein. In human liver (n)3)microsomes, the meanKmandVmaxvalues of SOH were 5.7(1.2 mM and 0.14(0.03µmol/min/nmol P450, respectively. The mean intrinsic clearance (Vmax/Km)was 25.3(2.3µL/min/nmol P450. SOH was sensitive to the inhibition by a CYP2C9 inhibitor, sulfaphenazole, and CYP2E1 inhibitors, 4-methylpyrazole and diethyldithiocarbamate. The liver microsomal SOH activity showed significant correlations with tolbutamide hydroxylation (r )0.569)and chlorzoxazone hydroxylation (r )0.770)activities, which were the model reactions catalyzed by CYP2C9 and CYP2E1, respectively. Human CYP2C9 and CYP2E1 showed SOH activities at least 2-fold higher than the other P450s. CYP2E1 showed an intrinsic clearance 3-fold greater than CYP2C9. These results demonstrated that CYP2C9 and CYP2E1 were the main P450s involved in human hepatic SOH.
700	1	2	_aUeng, Yune-Fang
700	1	2	_aHsieh, Chih-Hang
700	1	2	_aDon, Ming-Jaw
700	1	2	_aChi, Chin-Wen
700	1	2	_aHo, Li-Kang
856	4	0	_uhttps://drive.google.com/file/d/1haFdDQ2z7NqBRWSueJ30BMd-NR-Mbf_b/view?usp=drivesdk _zPara ver el documento ingresa a Google con tu cuenta: @cicy.edu.mx
942			_2Loc _cREF1
008			250602s9999 xx |||||s2 |||| ||und|d
999			_c52894 _d52894