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含铁血光活性一氧化碳释放复合物——HL-60细胞中的遗传毒性及诱导HO-1基因的能力

Photoactive CO-releasing complexes containing iron - genotoxicity and ability in HO-1 gene induction in HL-60 cells.

作者信息

Wysokiński Daniel, Lewandowska Patrycja, Zątak Daria, Juszczak Michał, Kluska Magdalena, Lizińska Daria, Rudolf Bogna, Woźniak Katarzyna

机构信息

Department of Molecular Genetics , Faculty of Biology and Environmental Protection , University of Lodz , 90-236 , Lodz , Poland . Email:

Department of Organic Chemistry , Faculty of Chemistry , University of Lodz , 91-403 Lodz , Poland.

出版信息

Toxicol Res (Camb). 2019 May 22;8(4):544-551. doi: 10.1039/c9tx00070d. eCollection 2019 Jul 1.

Abstract

This paper presents the results of research on the biological properties of two photoactive CO-releasing molecules containing iron, (η-CH)Fe(CO)(η--maleimidato) (complex ) and (η-CH)Fe(CO)(η--succinimidato) (complex ). We studied their cytotoxicity, genotoxicity and the ability of inducing the HO-1 gene in HL-60 cells. We also investigated the kinetics of DNA damage repair induced by complexes and . We demonstrated that complex was not toxic to HL-60 cells in high doses (above 100 μM). The ability to induce DNA damage was higher for complex . Importantly, there was no difference in irradiated and non-irradiated cells for both complexes. DNA damage induced by complex was repaired efficiently, while the repair of DNA damage induced by complex was disturbed. Complex had a minor effect on HO-1 gene expression (less than 2-fold induction), while complex had induced HO-1 gene expression to a great extent (over 17-fold for 10 μM) - similarly in irradiated and non-irradiated HL-60 cells. The results of our research indicate that the ability of both complexes to damage DNA and to upregulate HO-1 gene expression is not related to the release of CO. Further research is needed to test whether these compounds can be considered as potential CO carriers in humans.

摘要

本文介绍了对两种含铁的光活性一氧化碳释放分子(η-CH)Fe(CO)(η-马来酰亚胺基)(配合物)和(η-CH)Fe(CO)(η-琥珀酰亚胺基)(配合物)生物学特性的研究结果。我们研究了它们的细胞毒性、遗传毒性以及在HL-60细胞中诱导HO-1基因的能力。我们还研究了配合物和诱导的DNA损伤修复动力学。我们证明,高剂量(高于100μM)时配合物对HL-60细胞无毒。配合物诱导DNA损伤的能力更强。重要的是,两种配合物在辐照和未辐照细胞中均无差异。配合物诱导的DNA损伤能有效修复,而配合物诱导的DNA损伤修复受到干扰。配合物对HO-1基因表达影响较小(诱导倍数小于2倍),而配合物在很大程度上诱导了HO-1基因表达(10μM时超过17倍)——在辐照和未辐照的HL-60细胞中情况类似。我们的研究结果表明,两种配合物损伤DNA和上调HO-1基因表达的能力与CO的释放无关。需要进一步研究以测试这些化合物是否可被视为人类潜在的CO载体。

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