Suppr超能文献

天然化学预防剂异硫氰酸苄酯的遗传毒性效应

Genotoxic effects of benzyl isothiocyanate, a natural chemopreventive agent.

作者信息

Kassie F, Pool-Zobel B, Parzefall W, Knasmüller S

机构信息

Institute for Cancer Research, Borschkegasse 8a, A-1090 Vienna, Austria.

出版信息

Mutagenesis. 1999 Nov;14(6):595-604. doi: 10.1093/mutage/14.6.595.

Abstract

Benzyl isothiocyanate (BITC) is contained in cruciferous plants which are part of the human diet. Numerous reports indicate that BITC prevents chemically induced cancer in laboratory animals and it has been postulated that BITC might also be chemoprotective in humans. On the other hand, evidence is accumulating that this compound is a potent genotoxin in mammalian cells by itself. To further elucidate the potential hazards of BITC, we investigated its genotoxic effects in different in vitro genotoxicity tests and in animal models. In in vitro experiments [differential DNA repair assay with Escherichia coli, micronucleus assay with human HepG2 cells and single cell gel electrophoresis (SCGE) assay with hepatocytes and gastrointestinal tract cells] pronounced dose-dependent genotoxic effects were found at low dose levels (</=5 microg/ml). In contrast, substantially weaker effects were obtained in in vivo experiments with laboratory rodents: in the differential DNA repair assay with E.coli cells, only moderate genotoxic effects were seen in indicator cells recovered from various organs of mice after treatment with high doses (between 90 and 270 mg/kg), while in SCGE assay with rats a change in the DNA migration pattern was seen at a dose level of 220 mg/kg body wt. These findings indicate that BITC is detoxified under in vivo test conditions. This assumption was supported by the results of in vitro experiments which showed that the genotoxic effects of BITC are markedly reduced by bovine serum albumin and human body fluids such as saliva and gastric juice. Additional experiments carried out on the mechanistic aspects of the genotoxicity of BITC showed that this compound causes formation of thiobarbituric acid-reactive substances in HepG2 cells and that its DNA damaging properties are diminished by alpha-tocopherol, vitamin C, sodium benzoate and beta-carotene, indicating the possible involvement of free radicals in the genotoxicity of BITC. The doses of BITC required to cause measurable DNA damage in laboratory rodents exceeded by far the dietary exposure levels of humans, but are similar to those which were required to inhibit chemically induced cancer in earlier animal experiments.

摘要

异硫氰酸苄酯(BITC)存在于十字花科植物中,而十字花科植物是人类饮食的一部分。大量报告表明,BITC可预防实验动物的化学诱导癌症,据推测,BITC对人类可能也具有化学保护作用。另一方面,越来越多的证据表明,该化合物本身在哺乳动物细胞中是一种强效基因毒素。为了进一步阐明BITC的潜在危害,我们在不同的体外遗传毒性试验和动物模型中研究了其遗传毒性作用。在体外实验中[用大肠杆菌进行的差异DNA修复试验、用人肝癌细胞系HepG2进行的微核试验以及用肝细胞和胃肠道细胞进行的单细胞凝胶电泳(SCGE)试验],在低剂量水平(≤5微克/毫升)发现了明显的剂量依赖性遗传毒性作用。相比之下,在实验室啮齿动物的体内实验中获得的效应要弱得多:在用大肠杆菌细胞进行的差异DNA修复试验中,在用高剂量(90至270毫克/千克)处理后,从小鼠各个器官回收的指示细胞中仅观察到中等程度的遗传毒性作用,而在用大鼠进行的SCGE试验中,在体重剂量为220毫克/千克时观察到DNA迁移模式的变化。这些发现表明,BITC在体内试验条件下被解毒。这一假设得到了体外实验结果的支持,体外实验表明,牛血清白蛋白以及唾液和胃液等人的体液可显著降低BITC的遗传毒性作用。关于BITC遗传毒性机制方面的其他实验表明,该化合物在HepG2细胞中会导致硫代巴比妥酸反应性物质的形成,并且其DNA损伤特性会被α-生育酚、维生素C、苯甲酸钠和β-胡萝卜素减弱,这表明自由基可能参与了BITC的遗传毒性作用。在实验室啮齿动物中导致可测量的DNA损伤所需的BITC剂量远远超过人类的饮食暴露水平,但与早期动物实验中抑制化学诱导癌症所需的剂量相似。

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验