To Stress or Not To Stress: Pesticides and Cellular Stress Response
The results of several studies showed that the effects of pesticides, particularly glyphosate, on humans and animals, are not significant, but the results of a combination of studies showed no effect on granule formation or stress.
Abstract
Pesticides are nearly ubiquitous in our environment, due in part to their excessive use in agriculture. Two of the most heavily used pesticides are the herbicides N-‐ phosphonomethyl glycine (glyphosate) and 2,4-‐Dichlorophenoxyacetic acid (2,4-‐D). While several studies have examined the effects of glyphosate and 2,4-‐D on processes such as cell death and endocrine signaling in humans, the effects of these compounds on the cellular stress response were unknown. In this work, we have examined the effects of glyphosate and 2,4-‐D on the formation of stress granules, subcellular aggregates of translationally-‐ silent mRNP complexes that form under acute stress conditions. We find that the pesticide 2,4-‐D forms stress granules in a dose-‐responsive fashion in human osteosarcoma cells at concentrations ranging from 1 mM to 4 mM; glyphosate showed no stress granule formation at doses ranging from 1 mM to 100 mM, though cell death was observed at doses above 5 mM. We further show that 2,4-‐D-‐induced stress granules are blocked by pre-‐ treatment with the translation inhibitor cyclohexamide, thus confirming the mechanism of stress granule formation as dependent on polysome disassembly. Given the commonality of pesticide mixtures, glyphosate pre-‐treatments were performed to determine if glyphosate would induce or suppress stress granule formation in combination with 2,4-‐D, however no significant effect was observed. Our results show that 2,4-‐D may have a significant impact on cellular stress pathways, and that additional research into the effects of pesticides on the cellular stress response is warranted.