TY - JOUR
T1 - Polycyclic aromatic hydrocarbons disrupt axial development in sea urchin embryos through a β-catenin dependent pathway
AU - Pillai, Murali C.
AU - Vines, Carol A.
AU - Wikramanayake, Athula H.
AU - Cherr, Gary N.
N1 - Funding Information:
This research was funded in part by the University of California Toxic Substances Research and Teaching Program (Coastal Toxicology Component) and the Pacific Estuarine Ecosystem Indicator Research Consortium (PEEIR), Grant #R-82867601, which is part of US EPA's STAR EaGLe Program, and a sabbatical leave award (to M.C. Pillai) from Sonoma State University. The authors acknowledge Amber Mortenson of the Bodega Marine Laboratory Summer Marine Biology course, as well as past UC Davis Pharmacology and Toxicology 230 course (‘Experimental Approaches to Problems in Coastal Toxicology’) students at the Bodega Marine Laboratory who all made important observations leading to the initiation of this study.
PY - 2003/4/15
Y1 - 2003/4/15
N2 - Sea urchin (Lytechinus anemesis) embryos were used as an experimental system to investigate the mechanisms of the developmental toxicity of creosote, one of the most widely used wood preserving chemicals, as well as some of its polycyclic aromatic hydrocarbon (PAH) constituents (phenanthrene, fluoranthene, fluorene, pyrene and quinoline). Data suggest that creosote and PAHs affect axial development and patterning in sea urchin embryos by disrupting the regulation of β-catenin, a crucial transcriptional co-activator of specific target genes in the Wnt/wg signaling pathway. When ciliated blastula stage embryos were exposed to these compounds, they developed into exogastrulae with completely evaginated archentera, demonstrating that these chemicals disrupt axial development and patterning. This response occurred in a dose-dependent fashion, with the EC50 of creosote for complete exogastrulation being 1.57 ppm, while the EC50s of the PAHs ranged from 0.41 ppm (2.0 μM) to 4.33 ppm (33.5 μM). Morphologically, the exogastrulae that developed from embryos exposed to creosote and PAHs appeared to be identical to those that resulted from exposure to lithium chloride, a classical agent known to induce vegetalization and exogastrulation in sea urchin embryos. Immunological studies using antibodies against β-catenin, a multi-functional protein known to be involved in cell-cell adhesion and cell fate specification during embryonic development, revealed high levels of nuclear accumulation of β-catenin by cells of creosote- and PAH-exposed embryos, irrespective of their positions in the developing embryo. Dissociated embryonic cells cultured in the presence of these agents rapidly responded in a similar fashion. Since β-catenin accumulation occurs in nuclei of several types of cancer cells, it is possible this may be a general mechanism by which PAHs affect a variety of different cell types.
AB - Sea urchin (Lytechinus anemesis) embryos were used as an experimental system to investigate the mechanisms of the developmental toxicity of creosote, one of the most widely used wood preserving chemicals, as well as some of its polycyclic aromatic hydrocarbon (PAH) constituents (phenanthrene, fluoranthene, fluorene, pyrene and quinoline). Data suggest that creosote and PAHs affect axial development and patterning in sea urchin embryos by disrupting the regulation of β-catenin, a crucial transcriptional co-activator of specific target genes in the Wnt/wg signaling pathway. When ciliated blastula stage embryos were exposed to these compounds, they developed into exogastrulae with completely evaginated archentera, demonstrating that these chemicals disrupt axial development and patterning. This response occurred in a dose-dependent fashion, with the EC50 of creosote for complete exogastrulation being 1.57 ppm, while the EC50s of the PAHs ranged from 0.41 ppm (2.0 μM) to 4.33 ppm (33.5 μM). Morphologically, the exogastrulae that developed from embryos exposed to creosote and PAHs appeared to be identical to those that resulted from exposure to lithium chloride, a classical agent known to induce vegetalization and exogastrulation in sea urchin embryos. Immunological studies using antibodies against β-catenin, a multi-functional protein known to be involved in cell-cell adhesion and cell fate specification during embryonic development, revealed high levels of nuclear accumulation of β-catenin by cells of creosote- and PAH-exposed embryos, irrespective of their positions in the developing embryo. Dissociated embryonic cells cultured in the presence of these agents rapidly responded in a similar fashion. Since β-catenin accumulation occurs in nuclei of several types of cancer cells, it is possible this may be a general mechanism by which PAHs affect a variety of different cell types.
KW - β-catenin
KW - Creosote
KW - Developmental toxicity
KW - Exogastrulation
KW - Polycyclic aromatic hydrocarbon
KW - Sea urchin embryo
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U2 - 10.1016/S0300-483X(02)00695-9
DO - 10.1016/S0300-483X(02)00695-9
M3 - Article
C2 - 12604173
AN - SCOPUS:0037447583
VL - 186
SP - 93
EP - 108
JO - Toxicology
JF - Toxicology
SN - 0300-483X
IS - 1-2
ER -