Marques Eduardo de Souza, Salles Daiane Bernardoni, Maistro Edson Luis
Programa de Pós-Graduação em Biologia Geral e Aplicada, Universidade Estadual Paulista (UNESP), Instituto de Biociências, Botucatu, SP, Brazil.
Universidade Estadual Paulista - UNESP - Faculdade de Filosofia e Ciências, Departamento de Fonoaudiologia, Marília, SP 17525-900, Brazil.
Toxicol Rep. 2015 Jan 27;2:268-274. doi: 10.1016/j.toxrep.2015.01.005. eCollection 2015.
6,7-Dihydroxycoumarin (6,7-HC) (aesculetin) is a natural and synthetic coumarin derivative of great interest for use by humans due to their potent antioxidant properties. Considering that there are no reports that assess the genetic toxicity of 6,7-HC, the aim of the present study was to investigate its genotoxic potential in terms of DNA damage in peripheral blood, liver, bone marrow and testicular cells of Swiss albino mice by the comet assay, and its clastogenic/aneugenic potential in bone marrow cells using the micronucleus test. In addition, the ability of 6,7-HC to modulate the genotoxic effects induced by doxorubicin (DXR) was also preliminarily evaluated. Cytotoxicity was assessed by scoring polychromatic (PCE) and normochromatic (NCE) erythrocytes' ratio. The test compound was administered orally at doses of 25, 50 and 500 mg kg isolated and also simultaneously to DXR (80 mg kg). The results showed that 6,7-HC did not induce significant DNA damage in any of the analyzed cells, and also did not show any significant increase in micronucleated PCE at the three tested doses. The PCE/NCE ratio indicated no cytotoxicity. Moreover, the extent of DNA damage induced by DXR decreased significantly only in peripheral blood and testicular cells, and only at the lowest dose of 6,7-HC.
6,7 - 二羟基香豆素(6,7 - HC)(七叶亭)是一种天然和合成的香豆素衍生物,因其强大的抗氧化特性而备受人类关注。鉴于尚无评估6,7 - HC遗传毒性的报告,本研究的目的是通过彗星试验研究其对瑞士白化小鼠外周血、肝脏、骨髓和睾丸细胞DNA损伤方面的遗传毒性潜力,以及使用微核试验研究其在骨髓细胞中的致断裂/致非整倍体潜力。此外,还初步评估了6,7 - HC调节阿霉素(DXR)诱导的遗传毒性作用的能力。通过对多染性(PCE)和正染性(NCE)红细胞比例进行评分来评估细胞毒性。受试化合物以25、50和500 mg/kg的剂量单独口服给药,也与DXR(80 mg/kg)同时给药。结果表明,6,7 - HC在任何分析的细胞中均未诱导显著的DNA损伤,并且在三个测试剂量下微核化PCE也未显示出任何显著增加。PCE/NCE比值表明没有细胞毒性。此外,仅在最低剂量的6,7 - HC作用下,DXR诱导的DNA损伤程度在仅外周血和睾丸细胞中显著降低。