Modulation of rat pulmonary carcinogen-metabolising enzyme systems by the isothiocyanates erucin and sulforaphane
Modulation of rat pulmonary carcinogen-metabolising enzyme systems by the isothiocyanates erucin and sulforaphane
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DOI：
10.1016/j.cbi.2008.08.015
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发表时间：
2009-01-27
影响因子：
5.1
通讯作者：
Ioannides, Costas
中科院分区：
文献类型：
--
作者：
Hanlon, Natalya;Coldham, Nick;Ioannides, Costas
本研究的目的是评估脂肪族异硫氰酸酯、芥子蛋白和萝卜硫素对大鼠肺内肺癌代谢酶系统的潜在调节作用，而肺是其化学预防活性的靶器官。制备大鼠肺切片，分别加入不同浓度的芥菜素或萝卜硫素，孵育24小时。这两种化合物均不影响乙氧基苯并呋喃的O-脱乙基化，但显著提高细胞色素P450_1A1和细胞色素P450_1B_1的载脂蛋白水平。这两种化合物都不影响戊氧基间苯二酚的O-去戊基化和细胞色素P450_2B的载脂蛋白水平，但萝卜硫醚使细胞色素P3A2的载脂蛋白水平略有增加。以3-(4，5-dimethylthiazo-2-yl)-2，5-diphenyltetrazolium溴化物为底物监测的肺醌还原酶活性，被两种化合物显著上调，并与类似的蛋白质水平上升相平行。以1-氯-2，4-二硝基苯为接受底物，两种化合物均可提高细胞内谷胱甘肽S转移酶的活性；免疫学测定的GSTα蛋白水平略有上升，而GST pi水平不受相同处理的影响。最后，芥子素和萝卜硫素都增加了肺胞浆中总谷胱甘肽的浓度。结论：这些脂肪族异硫氰酸酯可能通过刺激其DNA结合的遗传毒性代谢物的原位解毒来拮抗肺癌致癌物的致癌作用。(C)2008爱思唯尔爱尔兰有限公司。保留所有权利。
The objective of this study was to evaluate the potential or the structurally related aliphatic isothiocyanates erucin and sulforaphane to modulate the pulmonary carcinogen-metabolising enzyme systems in rat lung, a target organ of their chemopreventive activity. Precision-cut rat lung slices were prepared and incubated for 24 h with a range of concentrations of either erucin or sulforaphane, Lip to 50 mu M. Neither compound modulated the O-deethylation of ethoxyresorufin whereas they elevated markedly CYP1A1 and, to a lesser extent, CYP1B1 apoprotein levels. Neither Compound influenced the O-depentylation of pentoxyresorufin or CYP2B apoprotein levels, but sulforaphane Caused a modest increase in CYP3A2 apoprotein levels. Pulmonary quinone reductase activity, monitored using 3-(4,5-dimethylthiazo-2-yl)-2,5-diphenyltetrazolium bromide as substrate, was markedly up-regulated by both Compounds and was paralleled by a similar rise in protein levels. Both compounds increased cytosolic glutathione S-transferase activity, measured using 1 -chloro-2,4-dinitrobenzene as the accepting substrate; a modest rise was seen in GST alpha protein levels, determined immunologically, whereas GST pi levels were un-affected by the same treatment. Finally,both erucin and sulforaphane increased total glutathione concentration in lung cytosol. It is concluded that these aliphatic isothiocyanates have the potential to antagonise the carcinogenicity of pulmonary carcinogens by stimulating the in situ detoxication of their DNA-binding genotoxic metabolites. (C) 2008 Elsevier Ireland Ltd. All rights reserved.