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芳烃应答小鼠对β-萘黄酮诱导的苯并[a]芘和黄曲霉毒素B1代谢及诱变的差异敏感性。

Differential sensitivity of Ah-responsive mice to beta-naphthoflavone-induced metabolism and mutagenesis of benzo[a]pyrene and aflatoxin B1.

作者信息

Raina V, Koser P, Gurtoo H L

出版信息

J Toxicol Environ Health. 1985;16(2):255-61. doi: 10.1080/15287398509530738.

DOI:10.1080/15287398509530738
PMID:3935808
Abstract

Effects of the administration to C57BL/6ha (Ah-responsive) mice of a low (10 mg/kg) and a high dose (150 mg/kg) of beta-naphthoflavone (BNF) on the hepatic microsome-mediated mutagenesis and metabolism of benzo[a]pyrene (BP) and aflatoxin B1 (AFB1) were studied. Hepatic microsome-mediated mutagenesis of benzo[a]pyrene was not enhanced by the low dose (10 mg/kg) but at the high dose (150 mg/kg) the mutagenic activation was enhanced several fold relative to control (corn oil-treated). Mutagenic activity of aflatoxin B1 was however depressed by both the low and the high doses of beta NF. These results are consistent with the effects of beta NF administration on hepatic microsome-mediated metabolism of BP to its phenolic products and on the metabolism of aflatoxin B1 to aflatoxin M1 catalyzed by aflatoxin B1-4-hydroxylase. Relative to control, pretreatment of the mice with 10 mg/kg beta NF did not induce aryl hydrocarbon hydroxylase activity (a measure of BP metabolism), however, the same pretreatment induced the metabolism of AFB1 to AFM1 by 2.7 to 4.7-fold. Microsomal preparations from 150 mg/kg beta NF-pretreated mice showed a 3-fold induction of aryl hydrocarbon hydroxylase activity and a 6.8-fold induction of AFB1-4-hydroxylase activity. These results suggest that two different enzyme systems are involved in the metabolism of BP and the metabolism of AFB1 to AFM1.

摘要

研究了低剂量(10毫克/千克)和高剂量(150毫克/千克)的β-萘黄酮(BNF)对C57BL/6ha(Ah反应型)小鼠肝脏微粒体介导的苯并[a]芘(BP)和黄曲霉毒素B1(AFB1)诱变和代谢的影响。低剂量(10毫克/千克)的β-萘黄酮未增强肝脏微粒体介导的苯并[a]芘诱变作用,但高剂量(150毫克/千克)时,诱变活化相对于对照组(玉米油处理组)增强了几倍。然而,低剂量和高剂量的β-萘黄酮均降低了黄曲霉毒素B1的诱变活性。这些结果与β-萘黄酮给药对肝脏微粒体介导的BP代谢为其酚类产物以及对黄曲霉毒素B1经黄曲霉毒素B1-4-羟化酶催化代谢为黄曲霉毒素M1的影响一致。相对于对照组,用10毫克/千克的β-萘黄酮预处理小鼠未诱导芳烃羟化酶活性(BP代谢的一种指标),然而,相同的预处理使AFB1代谢为AFM1的量增加了2.7至4.7倍。来自用150毫克/千克β-萘黄酮预处理小鼠的微粒体制剂显示芳烃羟化酶活性诱导了3倍,AFB1-4-羟化酶活性诱导了6.8倍。这些结果表明,BP代谢和AFB1代谢为AFM1涉及两种不同的酶系统。

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