Background:Humans are commonly exposed to multiple environmental chemicals, including tetrabromobisphenol A (TBBPA; a flame retardant), triclosan (an antimicrobial agent), and bisphenol A (BPA; polycarbonate plastics). These chemicals are readily absorbed and may interact with each other.Objectives:We sought to determine whether TBBPA, given alone or in combination with triclosan, can modulate the concentrations of BPA and 17β-estradiol (E2).Methods:Female and male CF-1 mice were each given a subcutaneous injection of 0–27mg TBBPA, with or without concurrent 0.33mg triclosan, followed by dietary administration of 50μg/kg body weight 14C-BPA. Radioactivity was measured in blood serum and tissues through liquid scintillation counting. In subsequent experiments, female and male CF-1 mice were each given a subcutaneous injection of 0 or 1mg TBBPA and E2 was measured in urine 2–12 h after injection.Results:Doses as low as 1mg TBBPA significantly elevated 14C-BPA concentrations in the uterus and ovaries of females; in the testes, epididymides, vesicular-coagulating glands, and preputial glands of males; and in blood serum, heart, lungs, and kidneys of both sexes; urinary E2 concentrations were also elevated. Lower doses of TBBPA or triclosan that had no effects on their own elevated 14C-BPA concentrations when the two substances were given concurrently.Conclusion:These data indicate that TBBPA, triclosan, and BPA interact in vivo, consistent with evidence that TBBPA and triclosan inhibit enzymes that are critical for BPA and E2 metabolism. https://doi.org/10.1289/EHP1329
The activation of the growth arrest-specific (gas) p20K gene depends on the interaction of C/EBP with two elements of a 48-bp promoter region termed the quiescence-responsive unit (QRU). Here we identify extracellular signal-related kinase 2 (ERK2) as a transcriptional repressor of the p20K QRU in cycling chicken embryo fibroblasts (CEF). ERK2 binds to repeated GAAAG sequences overlapping the C/EBP sites of the QRU. The recruitment of ERK2 and C/EBP is mutually exclusive and dictates the expression of p20K. C/EBP homologous protein (CHOP) was associated with C/EBP under conditions promoting endoplasmic reticulum (ER) stress and, to a lesser extent, in cycling CEF but was not detectable when C/EBP was immunoprecipitated from contact-inhibited cells. During ER stress, overexpression of CHOP inhibited p20K, while its downregulation promoted p20K, indicating that CHOP is also a potent inhibitor of p20K. Transcriptome analyses revealed that hypoxia-responsive genes are strongly induced in contact-inhibited but not serum-starved CEF, and elevated levels of nitroreductase activity, a marker of hypoxia, were detected at confluence. Conditions of hypoxia (2% O 2 ) induced growth arrest in subconfluent CEF and markedly stimulated p20K expression, suggesting that the control of proliferation and gas gene expression is closely linked to limiting oxygen concentrations associated with high cell densities.
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