Department of Natural Sciences, The University of Virginia's College at Wise, 1 College Avenue, Wise, VA, 24293.
Department of Natural Sciences, The University of Virginia's College at Wise, 1 College Avenue, Wise, VA, 24293
Biosci Rep. 2019 Jul 15;39(7). doi: 10.1042/BSR20190378. Print 2019 Jul 31.
Ruthenium organometallic compounds represent an attractive avenue in developing alternatives to platinum-based chemotherapeutic agents. While evidence has been presented indicating ruthenium-based compounds interact with isolated DNA , it is unclear what effect these compounds exert in cells. Moreover, the antibiotic efficacy of polynuclear ruthenium organometallic compounds remains uncertain. In the present study, we report that exposure to polynuclear ruthenium organometallic compounds induces recruitment of damaged DNA sensing protein Group C into chromatin-immobilized foci. Additionally, we observed one of the tested polynuclear ruthenium organometallic compounds displayed increased cytotoxicity against human cells deficient in nucleotide excision repair (NER). Taken together, these results suggest that polynuclear ruthenium organometallic compounds induce DNA damage in cells, and that cellular resistance to these compounds may be influenced by the NER DNA repair phenotype of the cells.
钌有机金属化合物是开发替代铂类化疗药物的一种有吸引力的方法。虽然有证据表明基于钌的化合物与分离的 DNA 相互作用,但这些化合物在细胞中产生什么影响还不清楚。此外,多核钌有机金属化合物的抗生素功效仍然不确定。在本研究中,我们报告暴露于多核钌有机金属化合物诱导损伤 DNA 感应蛋白 C 组募集到染色质固定焦点中。此外,我们观察到测试的一种多核钌有机金属化合物对核苷酸切除修复 (NER) 缺陷的人类细胞表现出增加的细胞毒性。总之,这些结果表明多核钌有机金属化合物在细胞中诱导 DNA 损伤,并且细胞对这些化合物的抗性可能受细胞 NER DNA 修复表型的影响。