■5-氟尿嘧啶(5-FU)和甲氨蝶呤(MTX)是全球最常用的抗肿瘤药物。考虑到细胞毒性,这些药物表现出低特异性,不仅会对癌细胞造成损害,还会对生物体内的健康细胞造成损害。在被消耗和代谢后,这些药物通过尿液和粪便排出体外,其次是废水处理。然而,传统的治疗方法没有能力完全去除这些物质,冒着将它们引入淡水系统的风险。即使在低浓度下,这也可能对人类健康构成风险。
■因此,本研究旨在研究遗传毒性,细胞毒性,5-FU和MTX在环境相关浓度下长期暴露后的致突变性,以成年雄性大鼠为实验模型。
■雄性Wistar大鼠(70日龄)分为4组(n=10/组):对照组,只收到车辆;MTX,在10ngL-1接受甲氨蝶呤;5-FU在10ngL-1接受5-氟尿嘧啶;和MTX+5-FU,分别在10ngL-1时接受MTX和5-FU的组合。暴露时间是从出生后的第70天(PND)到PND160,通过饮用水。之后,将动物安乐死,样品(肝脏,睾丸,股骨髓,和外周血)。
■在外周血中观察到DNA片段增加,肝脏,和睾丸,在彗星测定中改变尾矩和尾强度的参数。此外,PCE与NCE比值的变化提示骨髓抑制。
■这些发现警告了全球范围内长期暴露于痕量浓度的这些药物对普通人群的不利影响。
UNASSIGNED: 5-fluorouracil (5-FU) and methotrexate (MTX) are the antineoplastic drugs most commonly used worldwide. Considered cytotoxic, these pharmaceuticals exhibit low specificity, causing damage not only to cancer cells but also to healthy cells in organisms. After being consumed and metabolized, these drugs are excreted through urine and feces, followed by wastewater treatment. However, conventional treatments do not have the capacity to completely remove these substances, risking their introduction into freshwater systems. This could pose a risk to human health even at low concentrations.
UNASSIGNED: Thus, the present study aimed to investigate the genotoxicity, cytotoxicity, and mutagenicity of 5-FU and MTX at environmentally relevant concentrations after a long-term exposure, using adult male rats as an experimental model.
UNASSIGNED: Male Wistar rats (70 days old) were distributed into 4 groups (n = 10/group): control, received only vehicle; MTX, received methotrexate at 10ngL-1; 5-FU received 5-fluorouracil at 10ngL-1; and MTX + 5-FU, received a combination of MTX and 5-FU at 10ngL-1 each. The period of exposure was from postnatal day (PND) 70 to PND 160, through drinking water. After that, the animals were euthanized and the samples (liver, testis, femoral bone marrow, and peripheral blood) were obtained.
UNASSIGNED: Increased DNA fragmentation was observed in the peripheral blood, liver, and testis, altering the parameters of the tail moment and tail intensity in the Comet assay. Besides, the change in the ratio between PCE and NCE indicates bone marrow suppression.
UNASSIGNED: These findings warn the adverse effects for the general population worldwide chronically exposed to these drugs at trace concentration unintentionally.