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叶绿酸抗 N-甲基-N'-硝基-N-亚硝胍(MNNG)或 7,12-二甲基苯(α)蒽(DMBA)诱发哺乳动物细胞体外和体内微核的比较研究。

A comparative study of the anticlastogenic effects of chlorophyllin on N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) or 7,12-dimethylbenz (α) anthracene (DMBA) induced micronuclei in mammalian cells in vitro and in vivo.

机构信息

Department of Ecological and Biological Sciences, Università degli Studi della Tuscia, Largo dell'Università, snc, I-01100 Viterbo, Italy.

出版信息

Toxicol Lett. 2012 Nov 15;214(3):235-42. doi: 10.1016/j.toxlet.2012.08.023. Epub 2012 Sep 15.

Abstract

Chlorophyllin (CHL), a water soluble derivative of chlorophyll has been shown to have both anticarcinogenic and antigenotoxic properties. We evaluated the protective effects of CHL (25μM in vitro, 4 and 100mg/kg. b.w.) on the clastogenic action of two model carcinogens, MNNG and DMBA (25μM and 2μM respectively) in vitro on human hepatoma cells (HepG2) and (40mg and 25mg/Kg/b.w. respectively) in vivo on bone marrow of mice, using the frequencies of induced micronuclei as the end point. Pre-, post- and simultaneous treatments with CHL and the carcinogen were carried out in vitro. With MNNG, only simultaneous treatment with CHL was effective in reducing the frequencies of MN, suggesting a direct interaction between CHL and MNNG. A statistically significant reduction in of DMBA induced MN was found by pre-or post treatment with CHL while a reduction (not significant) was observed by simultaneous treatment. In in vivo experiments, CHL pre-treatment did not affect the frequencies of MN in PCEs of bone marrow induced by MNNG or DMBA. However, increased the toxic effect of DMBA (reduction in percent of PCEs) was accompanied by a reduction in the induced frequencies of MN. CHL was not clastogenic in both in vitro and in vivo tests. It can be concluded that (a) CHL has a protective effect against MNNG and DMBA. This effect is dependent upon the protocol employed in in vitro experiments. In vivo, CHL did not have a protective effect against MNNG and DMBA. A protective effect of CHL against DMBA was evident only at high toxic levels.

摘要

叶绿酸(CHL)是叶绿素的水溶性衍生物,已被证明具有抗癌和抗原毒性的特性。我们评估了 CHL(体外 25μM,体内 4 和 100mg/kg.b.w.)对两种模型致癌剂 MNNG 和 DMBA 的体外遗传毒性的保护作用(分别为 25μM 和 2μM)在体外人肝癌细胞(HepG2)和(分别为 40mg 和 25mg/Kg/b.w.)在体内小鼠骨髓中,以诱导微核的频率为终点。在体外进行了 CHL 与致癌剂的预、后和同时处理。对于 MNNG,只有同时用 CHL 处理才能有效降低 MN 的频率,这表明 CHL 与 MNNG 之间存在直接相互作用。用 CHL 进行预或后处理可显著降低 DMBA 诱导的 MN 频率,而同时处理则观察到降低(不显著)。在体内实验中,CHL 预处理不影响 MNNG 或 DMBA 诱导的骨髓嗜多染红细胞(PCE)中 MN 的频率。然而,增加 DMBA 的毒性作用(PCE 百分比降低)伴随着诱导的 MN 频率降低。CHL 在体内和体外实验中均无遗传毒性。可以得出结论:(a)CHL 对 MNNG 和 DMBA 具有保护作用。这种作用取决于体外实验中使用的方案。在体内,CHL 对 MNNG 和 DMBA 没有保护作用。CHL 对 DMBA 的保护作用仅在高毒性水平下明显。

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