BACKGROUND: Simazine is a triazine herbicide used worldwide in both agricultural and non-agricultural fields that is frequently detected in surface water and groundwater. Due to its widespread use, an increasing amount of research has focused on the potentially serious environmental and health risks.

MATERIAL AND METHODS: We used Western blotting and real-time quantitative PCR to analyze the effects of simazine on dopamine neuronal development-related factors in MN9D dopaminergic cells.

RESULTS: The expression of tyrosine hydroxylase (TH) mRNA was significantly increased after treatment with 300 and 600 μmol L–1 simazine after 24 and 48 h. Levels of nuclear-related receptor 1 (Nurr1) mRNA after 24- and 48-h exposure were decreased with 50 μmol L–1 simazine, but increased with 600 μmol L–1 simazine. Significant increases in TH and Nurr1 protein were observed in all simazine-treated groups at 24 and 48 h. The expression of neurogenin 2 and LIM homeobox transcription factor 1 beta (Lmx1b) mRNA were significantly increased after exposure to 600 μmol L–1 simazine for 48 h, while the expression of wingless-type MMTV integration site family member 1 (Wnt1) mRNA was increased by all doses of simazine.

CONCLUSIONS: Simazine may have an impact on TH in MN9D cells through 2 mechanisms; one mechanism is through the Lmx1a/Ngn2 pathway, and the other mechanism is through the Lmx1b-pitx3/Wnt1-Nurr1 pathway. These 2 pathways likely do not operate in isolation, but rather together, during the cellular response to simazine exposure.

Keywords: Cell Differentiation - physiology, Blotting, Western, Dopamine - metabolism, Dopaminergic Neurons - metabolism, Homeodomain Proteins - genetics, LIM-Homeodomain Proteins, Neurogenesis - drug effects, Nuclear Receptor Subfamily 4, Group A, Member 2 - metabolism, Simazine - toxicity, Transcription Factors, Tyrosine 3-Monooxygenase - genetics, Wnt1 Protein