Phthalate esters influence FGF-2 translocation in Py1a rat osteoblasts.
Exposure of the Py1a rat osteoblastic cells to butyl benzyl phthalate (BBP) and dibutyl phthalate (DBP) showed that these endocrine disrupting chemicals (EDC) strongly and reversibly affect the cytoplasmic fibroblast growth factor-2 (FGF-2) translocation into the nucleus in a dose-dependent and time-related manner. Stimulation of cells with high concentrations of BBP or DBP for short timing gave results comparable to those of cells treated with low concentrations for long timing. By confocal laser scanning microscope (CLSM) analysis it was found that the first relevant effect resulted in an accumulation of FGF-2 near the nuclear envelope, sometimes in the shape of clusters; the growth factor was then translocated into the nucleus and, finally, after long periods of exposure, the basal nuclear and cytoplasmic binding, typical of unstimulated cells, was re-established. In addition it was found that phthalate esters did not affect the FGF receptor 2 (FGFR-2) but decreased Con A binding indicating a possible inhibition of collagen fiber assembly. The different concentrations and timing of exposure of BBP and DBP affected the FGF-2 modulation in a similar way. Noticeable cumulative effects of BBP and DBP were not observed.
Menghi
G
G
Department of Comparative Morphological and Biochemical Sciences, University of Camerino, Italy. menghi@camserv.unicam.it
Sabbieti
M G
MG
Marchetti
L
L
Menghi
M
M
Materazzi
S
S
Hurley
M M
MM
D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D017364:Collagenases / Q000378:metabolism; D003208:Concanavalin A / Q000494:pharmacology; D003593:Cytoplasm / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004952:Esters / Q000494:pharmacology*; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D007150:Immunohistochemistry; D037102:Lectins / Q000494:pharmacology; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D010006:Osteoblasts / Q000378:metabolism*; D010795:Phthalic Acids / Q000494:pharmacology*; D011485:Protein Binding; D021381:Protein Transport; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D051497:Receptor, Fibroblast Growth Factor, Type 2; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism; D013997:Time Factors
D004952:Esters; D037102:Lectins; D010795:Phthalic Acids; D017468:Receptors, Fibroblast Growth Factor; D016222:Fibroblast Growth Factor 2; D003208:Concanavalin A; C032279:phthalic acid; C496356:Fgfr2 protein, rat; D020794:Receptor Protein-Tyrosine Kinases; D051497:Receptor, Fibroblast Growth Factor, Type 2; D017364:Collagenases