Impact of low-dose glyphosate and aminomethylphosphonic acid exposure on colorectal cancer sensitivity to 5-fluorouracil

Abstract

Colorectal cancer (CRC) may arise from a number of environmental pollutants from various origins including agriculture. Glyphosate is a wide-spectrum herbicide used worldwide. Its negative effects on the human body have been identified when exposure is in high doses and for short spans of time, yet little is known about its chronic low-dose exposure. Its main metabolite by the soil microbiome is aminomethylphosphonic acid (AMPA), the literary knowledge of which regarding its effects in the human body is lacking. In this study, the primary objectives are to identify a dose of glyphosate and AMPA that is sub-lethal yet effective in the CRC cell lines HCT116, DLD-1, and LoVo. The cells will then be exposed to this dose for two weeks and treated with concentrations of 5-fluorouracil (5-FU), in order to compare their viability to untreated cells. Lastly, protein expression analyses will be carried out using Western blotting and Enzyme linked immunosorbent assay (ELISA) to identify pathway mechanisms that may or may not have been activated. A sub-lethal dose of 5 μM glyphosate and AMPA was selected to be used for chronic exposure. Following chronic exposure, overall changes in viability were not significant between treated and untreated cells, however, notable changes were observed in glyphosate-treated cells at 50 μM 5- FU and in AMPA-treated cells at 5 μM 5-FU. Western blots were elusive, showing unwanted variations. ELISA outputs revealed a decrease in activated Epidermal Growth Factor Receptor (EGFR) in treated cells, indicating that EGFR downstream signalling pathways may have not been activated. Further research is needed to validate the reliability of the obtained results and to identify other possible mechanisms that respond to glyphosate and AMPA at low doses through protein expression analysis.