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草甘膦和氨甲基膦酸代谢物(AMPA)可调节小鼠黑色素瘤B16-F1细胞的表型。

Glyphosate and aminomethylphosphonic acid metabolite (AMPA) modulate the phenotype of murine melanoma B16-F1 cells.

作者信息

Salgado Kiefer Yvanna Carla de Souza, Ferreira Marianna Boia, da Luz Jessica Zablocki, Filipak Neto Francisco, Oliveira Ribeiro Ciro Alberto de

机构信息

Laboratório de Toxicologia Celular, Departamento de Biologia Celular, Universidade Federal do Paraná, Cx. Postal 19031, Curitiba, PR CEP 81.531-990, Brazil.

Laboratório de Toxicologia Celular, Departamento de Biologia Celular, Universidade Federal do Paraná, Cx. Postal 19031, Curitiba, PR CEP 81.531-990, Brazil.

出版信息

Environ Toxicol Pharmacol. 2024 Apr;107:104429. doi: 10.1016/j.etap.2024.104429. Epub 2024 Mar 26.

Abstract

Pesticides are contaminants run-offs from agricultural areas with a global concern due to their toxicity for non-target organisms. The Brazilian Health Surveillance Agency reported about 63% of the food contain pesticide residues. Glyphosate is a herbicide used worldwide but its toxicity is not a consensus among specialists around the world. AMPA (aminomethylphosphonic acid) is a glyphosate metabolite that can be more toxic than the parental molecule. Melanoma murine B16-F1 cells were exposed to glyphosate and AMPA to investigate the cell profile and possible induction to a more malignant phenotype. Glyphosate modulated the multi-drug resistance mechanisms by ABCB5 gene expression, decreasing cell attachment, increasing cell migration and inducing extracellular vesicles production, and the cells exposed to AMPA revealed potential damages to DNA. The present study observed that AMPA exhibits high cytotoxicity, which suggests a potential impact on non-tumor cells, which are, in general, more susceptible to chemical exposure. Conversely, glyphosate favored a more metastatic and chemoresistant behavior in cancer cells, highlighting the importance of additional research in this area.

摘要

农药是来自农业地区的污染物径流,由于其对非目标生物的毒性而受到全球关注。巴西卫生监督局报告称,约63%的食品含有农药残留。草甘膦是一种在全球范围内使用的除草剂,但其毒性在世界各地的专家中尚未达成共识。氨甲基膦酸(AMPA)是草甘膦的一种代谢产物,其毒性可能比母体分子更大。将黑色素瘤小鼠B16-F1细胞暴露于草甘膦和AMPA中,以研究细胞特征以及是否可能诱导出更恶性的表型。草甘膦通过ABCB5基因表达调节多药耐药机制,减少细胞附着,增加细胞迁移并诱导细胞外囊泡产生,而暴露于AMPA的细胞显示出对DNA的潜在损伤。本研究观察到AMPA具有高细胞毒性,这表明其对通常更容易受到化学物质暴露影响的非肿瘤细胞可能产生潜在影响。相反,草甘膦促使癌细胞表现出更具转移性和抗化疗的行为,凸显了该领域进一步研究的重要性。

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