Comparison of transcriptome alterations induced by pendimethalin or its commercial formulation Stomp Aqua in human MCF-7, MCF-10 A and MCF-12 A mammary epithelial cells

Objective: The toxicology of herbicides, which are currently in use is under-explored. One highly used but under investigated herbicide is pendimethalin. Here we mined high-throughput data from the US National Toxicology Program (NTP) to identify whether pendimethalin possesses an estrogenic capability in human cells. We also evaluated effects of pendimethalin and its reference commercial formulated herbicide Stomp Aqua on the transcriptome profile of three human mammary epithelial cell lines, cancerous MCF-7 and non-cancerous MCF-10 A and MCF-12 A to see whether this compound could have endocrine disrupting effects and if co-formulants present in the commercial formulation could amplify its toxicity.

Results: The data mined from the US NTP database suggests that pendimethalin activates estrogen receptors at a concentration of approximately 10?M. MCF-7, MCF-10A and MCF-12A cells were exposed to 10 ?M pendimethalin and Stomp Aqua at an equivalent concentration. Transcriptome analysis showed changes in gene expression patterns implying that pendimethalin affected ubiquitin-mediated proteolysis and the function of the spliceosome. The formulated pendimethalin product Stomp Aqua gave comparable effects suggesting pendimethalin was responsible for the observed transcriptome alterations. Given the lack of information on the exposure to this pesticide, our study prompts the need for biomonitoring studies, especially under occupational use scenarios, to understand if low level exposure to pendimethalin could have endocrine disrupting effects on populations exposed to this compound. A deeper understanding of the exposure and mechanisms of action of this endocrine-disrupting pesticide is needed.