Sarıgöl Kılıç Zehra, Çal Tuğbagül, Ündeğer Bucurgat Ülkü
Ammon Analytical Laboratory, Linden, USA.
Hacettepe University Faculty of Pharmacy, Department of Pharmaceutical Toxicology, Ankara, Turkey.
Turk J Pharm Sci. 2020 Dec 23;17(6):631-637. doi: 10.4274/tjps.galenos.2019.68725.
Herbicides are among the most widely used pesticide compounds for plant growth control worldwide. Risk assessment of the dinitroaniline-derived herbicides pendimethalin and trifluralin is important for foodborne or other means of exposure. In this study, we aimed to evaluate the methylation and acetylation profiles of pendimethalin and trifluralin, which we have high levels of exposure to in various ways. Furthermore, we also determined the protective effect of resveratrol, an antioxidant compound, against the possible toxic effects of these pesticides.
The effects of pendimethalin and trifluralin alone (25, 50, 100 μM) and in combination with resveratrol (100 μM) on DNA methyltransferase (DNMT1) 1, 3a, and 3b; and histone deacetylase () 1 and gene expression were evaluated by real-time polymerase chain reaction.
According to the results, pendimethalin caused a significant decrease in DNMT1, 3a, 3b and HDAC expressions at all concentrations, whereas HDAC1 and 3 expression was increased at the concentration of 25 μM, when applied together with resveratrol. There were no changes in DNMT1 or 3b expression levels. Unlike pendimethalin, trifluralin increased DNMT1 expression in a concentration-dependent manner. While DNMT3a and DNMT3b expression levels increased significantly, HDAC1 and 3 expression levels did not change significantly. The expression levels of HDAC1 and HDAC3 increased at all concentrations of trifluralin combination with resveratrol. Moreover, DNMT levels increased at the concentrations of 50 and 100 μM.
Epigenetic gene expression results showed that pendimethalin and trifluralin might cause tissue function loss and chromosome damage as a result of direct effects on cell viability by causing expression level changes in all studied genes. It can also be concluded that the changes that occur in gene expression may induce tumor development. Further studies are needed to elucidate the possible toxicity mechanisms of these herbicides, considering the relationship between epigenetic changes and various diseases.
除草剂是全球范围内用于控制植物生长的使用最为广泛的农药化合物之一。对二硝基苯胺类除草剂二甲戊灵和氟乐灵进行风险评估对于通过食源性或其他暴露途径的接触而言至关重要。在本研究中,我们旨在评估我们通过各种方式大量接触的二甲戊灵和氟乐灵的甲基化和乙酰化谱。此外,我们还确定了抗氧化化合物白藜芦醇对这些农药可能的毒性作用的保护作用。
通过实时聚合酶链反应评估单独使用二甲戊灵和氟乐灵(25、50、100μM)以及与白藜芦醇(100μM)联合使用对DNA甲基转移酶(DNMT1)1、3a和3b;以及组蛋白脱乙酰基酶(HDAC)1和HDAC3基因表达的影响。
根据结果,二甲戊灵在所有浓度下均导致DNMT1、3a、3b和HDAC表达显著降低,而当与白藜芦醇一起使用时,在25μM浓度下HDAC1和HDAC3表达增加。DNMT1或3b表达水平没有变化。与二甲戊灵不同,氟乐灵以浓度依赖性方式增加DNMT1表达。虽然DNMT3a和DNMT3b表达水平显著增加,但HDAC1和HDAC3表达水平没有显著变化。在氟乐灵与白藜芦醇联合使用的所有浓度下,HDAC1和HDAC3表达水平均增加。此外,在50和100μM浓度下DNMT水平增加。
表观遗传基因表达结果表明,二甲戊灵和氟乐灵可能通过导致所有研究基因的表达水平变化而直接影响细胞活力,从而导致组织功能丧失和染色体损伤。还可以得出结论,基因表达中发生的变化可能诱导肿瘤发展。考虑到表观遗传变化与各种疾病之间的关系,需要进一步研究以阐明这些除草剂可能的毒性机制。