Introducción. El glifosato es un herbicida de amplio espectro, no selectivo, utilizado para eliminar malezas indeseables en ambientes agrícolas y forestales. La acción herbicida corresponde a la inhibición de la biosíntesis de aminoácidos aromáticos en las plantas. Al no ser este mecanismo compartido por los seres humanos es considerado como de bajo riesgo para la salud de los mismos. Sin embargo, investigaciones recientes indican que puede alterar otros procesos celulares en animales lo que puede presentar un factor de riesgo a nivel ambiental y de salud en las zonas donde se emplea este herbicida. Objetivo. El objetivo del presente estudio fue evaluar la citotoxicidad y la genotoxicidad del glifosato en células humanas normales (GM38) y en células humanas de fibrosarcoma (HT1080). Materiales y métodos. La citotoxicidad aguda y crónica se determinó al exponer las células en cultivo a diferentes concentraciones de glifosato, y se analizó la viabilidad celular con cristal violeta y colorante de exclusión azul de tripano, respectivamente. La genotoxicidad se determinó por medio del ensayo del cometa y los datos se analizaron usando la prueba de Dunnet. Resultados. En la citotoxicidad crónica las células GM38 y las HT1080 presentaron un efecto dependiente de la dosis después del tratamiento con glifosato en concentraciones de 5,2 a 8,5 mM y 0,9 a 3,0 mM, respectivamente. En la citotoxicidad aguda, las células GM38 y las HT1080 expuestas a un rango de concentraciones de 4,0 a 7,0 mM, 4,5 a 5,75 mM y 4,0 a 7,0 mM, respectivamente, presentaron una viabilidad mayor al 80%. Se evidenció daño en el ADN después del tratamiento con glifosato en concentraciones de 4,0 a 6,5 mM para las células GM38 y de 4,75 a 5,75 mM para las células HT1080. Conclusiones. Se sugiere que el mecanismo de acción del glifosato no se limita únicamente a las plantas sino que puede alterar la estructura del ADN en otros tipos de células como son las de los mamíferos.Palabras clave: herbicidas, citotoxicidad, genotoxicidad, ensayo cometa. Cytotoxicity and genotoxicity of human cells exposed in vitro to glyphosateIntroduction. Glyphosate is a broad-spectrum non-selective herbicide, used to eliminate unwanted weeds in agricultural and forest settings. Herbicide action is achieved through inhibition of aromatic amino acid biosynthesis in plant cells. Since this is not a conserved mechanism between human and plant cells, glyphosate is considered to be a low health risk substance for humans. However, the occurrence of possible harmful side effects of glyphosate use is not well documented and controversial. Toxicity and genotoxicity studies indicate that glyphosate is not harmful, although several investigations suggest that it can alter various cellular processes in animals. Therfore this has potential as a health and environmental risk factor in areas where glyphosate is widely used.Objectives. The present study evaluated glyphosate cytotoxic and genotoxic effects in normal human cells (GM38) and human fibrosarcoma (HT1080) cells. Materials and method...

The p53 tumor‐suppressor gene has been implicated in the inducible activation of excision repair of ultraviolet (UV)‐induced cyclobutane pyrimidine dimers (CPDs) in human cells. Because the large T antigen (LTAg) of the simian virus 40 (SV40) binds p53 protein and can interfere with its function, it was of interest to study DNA repair in normal human fibroblasts that had been transformed by SV40 compared with that in their nontransformed parental counterparts and to determine whether such transformation attenuated global genomic repair (GGR) of CPDs. Three methods were used to measure GGR in UV‐irradiated cells: (i) an immunoassay using monoclonal antibodies specific for CPDs or 6‐4 photoproducts (6‐4PPs), (ii) zone sedimentation in alkaline sucrose gradients to measure the average DNA strand size after specific nicking at CPD sites in duplex DNA with T4 endonuclease V (TEV), and (iii) Southern hybridization of TEV‐treated DNA with strand‐specific mRNA probes to assess removal of CPDs from either strand of a defined genetic sequence in an expressed gene. Whereas repair of 6‐4PPs was very similar in paired SV40‐transformed and primary fibroblasts, GGR of CPDs was significantly reduced in the SV40‐transformed cells. In contrast, SV40 transformation did not appreciably affect the efficiency of transcription‐coupled repair. These data support the hypothesis that SV40 transformation can result in reduced levels of GGR, most likely because of the inhibition of normal p53 function by LTAg. Mol. Carcinog. 29:17–24, 2000. © 2000 Wiley‐Liss, Inc.

No abstract

The p53 tumor-suppressor gene has been implicated in the inducible activation of excision repair of ultraviolet (UV)-induced cyclobutane pyrimidine dimers (CPDs) in human cells. Because the large T antigen (LTAg) of the simian virus 40 (SV40) binds p53 protein and can interfere with its function, it was of interest to study DNA repair in normal human fibroblasts that had been transformed by SV40 compared with that in their nontransformed parental counterparts and to determine whether such transformation attenuated global genomic repair (GGR) of CPDs. Three methods were used to measure GGR in UV-irradiated cells: (i) an immunoassay using monoclonal antibodies specific for CPDs or 6-4 photoproducts (6-4PPs), (ii) zone sedimentation in alkaline sucrose gradients to measure the average DNA strand size after specific nicking at CPD sites in duplex DNA with T4 endonuclease V (TEV), and (iii) Southern hybridization of TEV-treated DNA with strand-specific mRNA probes to assess removal of CPDs from either strand of a defined genetic sequence in an expressed gene. Whereas repair of 6-4PPs was very similar in paired SV40-transformed and primary fibroblasts, GGR of CPDs was significantly reduced in the SV40-transformed cells. In contrast, SV40 transformation did not appreciably affect the efficiency of transcription-coupled repair. These data support the hypothesis that SV40 transformation can result in reduced levels of GGR, most likely because of the inhibition of normal p53 function by LTAg.

No abstract