Thus, the high number of possibilities in protein protein and protein-DNA contacts likely reflects the propensity of developmental TFs to regulate target gene expression in many different cell contexts.
We report that INR and FPR motifs usually occur separately, but come together as an INR plus FPR "supramotif" in 10-15% of promoters where they are linked to higher than average mRNA levels, an increased propensity towards developmental regulation, and gene functions related to pathogenesis.
These results indicate a complete dichotomy between the systemic toxicity of organophosphates and their propensity to elicit developmental neurotoxicity.
These agents are undergoing increased scrutiny specifically because of their propensity to elicit developmental neurotoxicity at levels below those required for any signs of systemic exposure (Colborn 2006; Costa 2006; Pope 1999; Slotkin 2004, 2005).
Accordingly, the relative potencies of organophosphates toward cholinesterase inhibition and/or systemic toxicity do not necessarily correlate with their propensity to elicit developmental neurotoxicity (Costa 2006; Pope 1999; Qiao et al. 2001; Slotkin et al. 2006a, 2006b).
The fact that there are similarities but also notable disparities in the responses to chlorpyrifos and diazinon, and that robust effects were seen at a dose of diazinon that does not inhibit cholinesterase, supports the idea that organophosphates differ in their propensity to elicit developmental neurotoxicity, unrelated to their anticholinesterase activity.
Exposure of the human population to organophosphate pesticides is ubiquitous (Barr et al. 2005; Bouvier et al. 2005; Casida and Quistad 2004), and these compounds are undergoing restriction because of their propensity to produce developmental neurotoxicity [ U.S. Environmental Protection Agency EPAA) 2000, 2002, 2006].
The major concern for CPF is its propensity to elicit developmental neurotoxicity at exposure levels below the threshold for systemic toxicity, such that damaging exposures of pregnant women and children may go undetected because of the lack of symptoms (Landrigan 2001; Landrigan et al. 1999; May 2000; Physicians for Social Responsibility 1995; Pope 1999; Slotkin 1999, 2004; Weiss et al. 2004).
However, compared with chlorpyrifos and diazinon, parathion exhibits greater systemic toxicity relative to its propensity to produce developmental neurotoxicity (Slotkin et al. 2006a), again echoing the view that organophosphates are distinct in their profiles for adverse effects on the immature brain.
The nearly ubiquitous exposure of the human population to organophosphate pesticides has raised increasing concern about their propensity to elicit developmental neurotoxicity at exposures that go undetected because of the absence of systemic signs of intoxication (Colborn 2006; Costa 2006; Landrigan 2001; Mileson et al. 1998; Slotkin 2005; Weiss et al. 2004).
