EFFECT OF ALACHLOR ON HEPATIC CYTOCHROME P450 ENZYMES IN RATS
EFFECT OF ALACHLOR ON HEPATIC CYTOCHROME P450 ENZYMES IN RATS
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乙草胺对大鼠肝细胞色素P450酶的影响
DOI：
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发表时间：
2002
期刊：
影响因子：
--
通讯作者：
M. Ando
中科院分区：
文献类型：
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作者：
N. Hanioka;Kayoko Watanabe;R. Yoda;M. Ando
甲草胺（（2-氯-N-甲氧基甲基）-N-（2，6-二乙基苯基）乙酰胺）是一种广泛使用的芽前除草剂，美国环保局已将其列为可能的人类致癌物。该除草剂可能通过肝细胞色素P450系统代谢。我们研究了甲草胺对大鼠肝微粒体细胞色素P450酶的影响。每天给大鼠腹腔注射甲草胺，剂量为25、50和100毫克/千克，连续5天。在依赖细胞色素P450的单加氧酶活性中，甲草胺以剂量依赖性方式增加了与CYP 2B 1相关的7-戊氧基试卤灵O-脱戊基酶。相对于对照活性的诱导为1.7-4.2倍。甲草胺在50和100毫克/千克的剂量下也显著增加了依赖CYP 1A的单加氧酶，如7-乙氧基试卤灵O-脱乙基酶和乙酰苯胺4-羟化酶的活性（1.7-2.1倍）。此外，免疫印迹显示，甲草胺使CYP 2B 1/2和CYP 1A 1/2蛋白水平分别显著增加4.2-6.3倍和1.8倍。较高剂量（≥ 50 mg/kg）的甲草胺对7-乙氧基香豆素O-脱乙基酶、丁呋洛尔1′-羟化酶和4-硝基苯酚2-羟化酶的活性有显著的促进作用，但诱导倍数均小于1.6倍。其他依赖细胞色素P450的单加氧酶，即睾酮7α-羟化酶、睾酮2α-羟化酶、睾酮6β-羟化酶和月桂酸ω-羟化酶的活性在任何剂量下都不受甲草胺的影响。此外，CYP 2C 11/6、CYP 2D 1、CYP 2 E1、CYP 3A 2/1和CYP 4A 1/2/3的蛋白水平无显著变化。这些结果表明，甲草胺选择性地诱导大鼠肝微粒体中CYP 1A和CYP 2B亚家族的细胞色素P450亚型，这些亚型的表达与甲草胺的毒性密切相关。
Alachlor ((2-chloro-N-methoxymethyl)-N-(2,6-diethylphenyl)acetamide) is a widely used preemergence herbicide which has been classified by the USEPA as a probable human carcinogen. The herbicide has been suggested to be metabolized by hepatic cytochrome P450 system. We examined the effects of alachlor on cytochrome P450 enzymes in rat liver microsomes. Rats were treated intraperitoneally with alachlor daily for 5 days, at doses of 25, 50 and 100 mg/kg. Among the cytochrome P450-dependent monooxygenase activities, 7-pentoxyresorufin O-depentylase, which is associated with CYP2B1, was dose-dependently increased by alachlor. The induction relative to control activity was 1.7–4.2-fold. The activities of CYP1A-dependent monooxygenases such as 7-ethoxyresorufin O-deethylase and acetanilide 4-hydroxylase were also significantly increased by alachlor at doses of 50 and 100 mg/kg (1.7–2.1-fold). Furthermore, immunoblotting showed that alachlor significantly increased CYP2B1/2 and CYP1A1/2 protein levels by 4.2–6.3- and 1.8-fold, respectively. Although 7-ethoxycoumarin O-deethylase, bufuralol 1′-hydroxylase and 4-nitrophenol 2-hydroxylase activities were significantly increased by alachlor at higher doses (≥ 50 mg/kg), the induction ratios were less than 1.6-fold. The activities of other cytochrome P450-dependent monooxygenases, namely testosterone 7α-hydroxylase, testosterone 2α-hydroxylase, testosterone 6β-hydroxylase and lauric acid ω-hydroxylase, were not affected by alachlor at any dose. In addition, there was no significant change in the protein levels of CYP2C11/6, CYP2D1, CYP2E1, CYP3A2/1 and CYP4A1/2/3. These results suggest that alachlor selectively induces cytochrome P450 isoforms of the CYP1A and CYP2B subfamilies in rat liver microsomes, and that the expression of these isoforms is closely related to the toxicity of alachlor.
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影响因子：
3.9
作者：
M. Tsutsumi;J. Lasker;T. Takahashi;Charles S. Lieber
通讯作者：
M. Tsutsumi;J. Lasker;T. Takahashi;Charles S. Lieber
人和大鼠肝微粒体中氯乙酰氨酰胺除草剂和选定的代谢产物的比较代谢。
影响因子：
10.4
作者：
Coleman S;Linderman R;Hodgson E;Rose RL
通讯作者：
Rose RL
影响因子：
2.9
作者：
WAXMAN, DJ;DANNAN, GA;GUENGERICH, FP
通讯作者：
GUENGERICH, FP
DOI：
10.1016/s1383-5718(97)00163-0
发表时间：
1997-12-12
影响因子：
1.9
作者：
Hill, AB;Jefferies, PR;Casida, JE
通讯作者：
Casida, JE