Differentiation state-dependent effects of in vitro exposure to atrazine or its metabolite diaminochlorotriazine in a dopaminergic cell line.

Aims: This study sought to determine the impact of in vitro exposure to the herbicide atrazine (ATR) or its major mammalian metabolite diaminochlorotriazine (DACT) on dopaminergic cell differentiation.

Main Methods: N27 dopaminergic cells were exposed for 24 or 48 h to ATR or DACT (12-300 μM) and their effects on cell viability, ATP levels, ADP:ATP ratio and differentiation markers, such as soma size and neurite outgrowth, were assessed.

Key Findings: Overall, intracellular ATP levels and soma size (decreased by ATR at ≥12 μM; 48 h) were the two parameters most sensitive to ATR exposure in undifferentiated and differentiating dopaminergic cells, respectively. At the morphological level, ATR, but not DACT, increased the percentage of morphologically abnormal undifferentiated N27 cells. On the other hand, exposure to DACT (300 μM; 48 h), but not ATR, increased the ADP:ATP ratio regardless of the differentiation state and it moderately disrupted thin neurite outgrowth. Only the highest concentration of ATR or DACT (300 μM) was cytotoxic after a longer exposure (48 h) and undifferentiated N27 cells were the least sensitive to the cytotoxic effects of ATR or DACT.

Significance: Our results suggest that the energy perturbation and morphological disruption of dopaminergic neuronal differentiation induced by ATR and, to a lesser extent, DACT, may be associated with reported neurological deficits caused by developmental ATR exposure in rodents.