Academic journal article Environmental Health Perspectives

Adverse Benzo[a]pyrene Effects on Neurodifferentiation Are Altered by Other Neurotoxicant Coexposures: Interactions with Dexamethasone, Chlorpyrifos, or Nicotine in PC12 Cells

Academic journal article Environmental Health Perspectives

Adverse Benzo[a]pyrene Effects on Neurodifferentiation Are Altered by Other Neurotoxicant Coexposures: Interactions with Dexamethasone, Chlorpyrifos, or Nicotine in PC12 Cells

Article excerpt

Exposures to polycyclic aromatic hydrocarbons (PAHs) are ubiquitous, given their presence in combustion products of all kinds, including diesel exhaust, broiled foods, and smoke arising from wood, coal, or tobacco. Although most studies of the adverse effects of PAHs center around their properties as carcinogens, recent reports have indicated that these agents are also developmental neurotoxicants, potentially contributing to the substantial increase in the incidence of neurobehavioral disorders (Grandjean and Landrigan 2006). Epidemiological studies show a relationship between fetal PAH exposure, head circumference, and cognitive performance (Perera et al. 2003, 2006), but few animal studies have explored whether these agents directly affect brain development. Benzo[

One major difference between laboratory and human PAH studies is that although basic research tends to focus on exposures to single agents, humans are simultaneously exposed to other developmental neurotoxicants along with the PAHs, such as tobacco smoke and pesticides (Perera et al. 2005). In the present study, we examined whether the direct effects of PAHs on neuronal development are modified by simultaneous exposure to other commonly encountered neurot oxicants. Specifically, we looked at the combination of BaP with a glucocorticoid (dexamethasone), an organophosphate pesticide (chlorpyrifos), and nicotine. Each of these secondary agents has been well-studied for developmental neurotoxicity in vivo and in vitro, and they all represent major human exposure hazards. Glucocorticoids are the consensus treatment for preterm labor occurring between 24 and 34 weeks of gestation in order to prevent respiratory distress syndrome (Gilstrap et al. 1995); currently, 1 of every 10 newborns in the United States has undergone this treatment (Matthews et al. 2002). Organophosphates represent nearly 50% of worldwide insecticide use, and exposure of the human population is virtually ubiquitous (Casida and Quistad 2004). Nicotine coexposure with PAHs is common because of the presence of both in cigarette smoke, whether from active maternal smoking or from second- and third-hand exposure (Hoh et al. 2012; Perera et al. 2005).

For our study, we used PC12 cells, a well-characterized model for neurodifferentiation (Teng and Greene 1994), with protocols established previously for characterizing developmental neurotoxicity (Qiao et al. 2001, 2003, 2005; Slotkin et al. 2007a, 2007b, 2008; Song et al. 1998). Effects on cell number were determined by measuring DNA content, because each neuronotypic cell contains only a single nucleus (Winick and Noble 1965). Cell size and membrane outgrowth associated with the formation of neurites were assessed by measurements of cell proteins (total protein/DNA ratio, membrane protein/DNA ratio, and membrane protein/total protein ratio). …

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