ODP272 ROUNDUP IS AN IMPORTANT DISRUPTOR THAT CAUSES PROLIFERATIVE EFFECTS ON NORMAL AND ON CANCER THYROID CELLS

Abstract

Abstract Glyphosate has long be suspected to promote endocrine disruptive and even carcinogenic effects, but little is known about its effect at different concentrations on normal and on cancer thyroid cells. Since the endocrine system responds to low chemical concentrations and abnormal cells may have different sensitivity, it is essential to determine the effects of this compound at different levels, including the Acceptable Occupational Exposure Level (AOEL) and the Acceptable Daily Intake (IDA) doses. We used two human thyroid-derived cell lines strains, Nthy-ori 3-1 (from thyroid normal follicular cells) and TPC-1 (from papillary carcinoma) to test 15 different concentrations of Roundup® Original DI, ranging from 6.5 µg/L to 6.500 µg/L, including AOEL and IDA according to the Technical Note Process No. 25351. 056754/2013-17 of the National Health Surveillance Agency (ANVISA) in Brazil. Trypan blue assay and Cell Counting Kit – 8 (CCK-8) were employed to evaluate cell viability and cytotoxicity. Exposures were made for 24 and 48 hours in technical and biological triplicates. We observed a decrease in the number of viable cells at the 24h exposure compared to 48h in both strains. Exposure of Nthy-ori 3-1 and TPC-1 cells for 24h at the AOEL concentration (160µg/L) caused death of 52% and 58% of the cells, respectively, whereas IDA (830µg/L) resulted in 43% e 58% cell death. These data evidence an important disruptive effect of Roundup Original DI® at the acceptable concentrations. After 48h of exposure, AOEL and IDA concentrations caused a lower number of Nthy-ori 3-1 (19% e 15%) and TPC-1 (29% e 23%) dead cells, respectively, suggesting both thyroid strains have compensatory mechanisms that protect them from longer exposures to the herbicide. The CCK-8 assay, on the contrary, showed a proliferative effect on small concentrations: 6.5 µg/L increased the number of viable Nthy-ori 3-1 and TPC-1 cells to 113% and 118%, respectively, at 24h, and this stimulatory effect persisted after 48h of exposure. In contrast, AOEL and IDA concentrations produced a reduction in the number of both strains cells, likewise observed with the Trypan blue assay. Our data demonstrate that thyroid cells exposed to Roundup Original DI® present a non-monotone dose-response curve, which is a well-known characteristic of an endocrine disruptor. The proliferative effect produced on thyroid cells, especially TPC-1 mutant cells, by very low concentrations of this glyphosate-based herbicide widely used around the world, suggests that it may play a role in the increasing incidence rate of thyroid nodules and/or cancer that have been observed worldwide. Presentation: No date and time listed