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邻苯二甲酸二(2-乙基己基)酯和邻苯二甲酸二丁酯的致裂、变倍体和微管聚合性质。

Clastogenic, aneugenic, and tubulin polymerization properties of di-(2-ethylhexyl) phthalate and dibutyl phthalate.

机构信息

Department of Applied Biology, CSIR-Indian Institute of Chemical Technology, Hyderabad, India.

Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India.

出版信息

Toxicol Ind Health. 2023 Sep;39(9):504-514. doi: 10.1177/07482337231182191. Epub 2023 Jul 12.

Abstract

Phthalate compounds were found to disrupt the endocrine system and alter transcriptomes during human embryonic development. In our previous work, we have isolated and reported two such phthalates di-(2-ethylhexyl) phthalate (DEHP) and dibutyl phthalate (DBP) from bacteria and evaluated their bioactive properties. Naturally derived phthalates might be less toxic compared with synthesized molecules. We have investigated biologically isolated phthalates to understand the possible genotoxic effects in mice and further investigated in silico binding and polymerization of β-tubulin. Three sub-lethal concentrations of DEHP (150 μM, 175 μM, and 200 μM) and DBP (10 μM, 15 μM, and 30 μM) were studied. The results showed that the phthalates were found to be highly genotoxic in nature. However, the pattern of genotoxic effects was not found to be dose-dependent in the induction of chromosome aberrations (CA), micronuclei (MN), and changes in the mitotic index (MI) in cells. studies of phthalates on polymerization of β-tubulin suggested that both DBP and DEHP were able to interact with the hydrogen bonds and make strong van der Waals interactions with β-tubulin thereby possibly causing destabilization of microtubule network. Our study suggests that these phthalates might be playing an important role in normal cell division thereby showing highly genotoxic effects.

摘要

邻苯二甲酸酯化合物被发现会在人类胚胎发育过程中干扰内分泌系统并改变转录组。在我们之前的工作中,我们已经从细菌中分离并报告了两种邻苯二甲酸酯,即邻苯二甲酸二(2-乙基己基)酯(DEHP)和邻苯二甲酸二丁酯(DBP),并评估了它们的生物活性。与合成分子相比,天然衍生的邻苯二甲酸酯可能毒性较小。我们已经研究了生物分离的邻苯二甲酸酯,以了解其在小鼠中的可能遗传毒性作用,并进一步研究了β-微管蛋白的结合和聚合的计算机模拟。研究了三种亚致死浓度的 DEHP(150 μM、175 μM 和 200 μM)和 DBP(10 μM、15 μM 和 30 μM)。结果表明,邻苯二甲酸酯具有高度的遗传毒性。然而,在诱导染色体畸变(CA)、微核(MN)和细胞有丝分裂指数(MI)变化方面,遗传毒性效应的模式并没有发现与浓度呈剂量依赖性。邻苯二甲酸酯对β-微管蛋白聚合的研究表明,DBP 和 DEHP 都能够与氢键相互作用,并与β-微管蛋白形成强范德华相互作用,从而可能导致微管网络的不稳定性。我们的研究表明,这些邻苯二甲酸酯可能在正常细胞分裂中发挥重要作用,从而表现出高度的遗传毒性。

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