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Bisphenol A and its methylated congeners inhibit growth and interfere with microtubules in human fibroblasts in vitro
Authors:Lehmann Leane  Metzler Manfred
Institution:Institute of Food Chemistry and Toxicology, University of Karlsruhe, P.O. Box 6980, Karlsruhe D-76128, Germany.
Abstract:Bisphenol A (BPA), a monomer of polycarbonate plastics and epoxy resins, has previously been reported to induce micronuclei containing whole chromosomes in Chinese hamster V79 cells. In the present study, the aneuploidogenic potential of BPA was investigated in cultured human AG01522C fibroblasts. In contrast to the known aneugens diethylstilbestrol (DES) and 17beta-estradiol, which caused mitotic arrest and the induction of kinetochore-positive micronuclei, BPA did not induce micronuclei and inhibited the proliferation of AG01522C cells in G2 phase and probably also in G1 phase. Fluorescence microscopy of the BPA-treated cells after immunofluorescent staining of microtubules revealed structural abnormalities of the cytoplasmic microtubule complex (CMTC): densely stained rings and loops of tubulin were observed, which increased in number with increasing BPA concentration and were more stable against low temperature than normal microtubules. The mechanisms of the growth inhibition and the interference with microtubules elicited by BPA in AG01522C cells are presently unknown. The formation of rings and loops in the CMTC of AG01522C cells was also observed with two congeners of BPA carrying one and two, respectively, additional methyl groups in ortho-position to the phenolic hydroxyl group at each aromatic ring. However, in contrast to BPA itself, these congeners of BPA behaved "DES-like" by inducing mitotic arrest and kinetochore-positive micronuclei in AG01522C cells.
Keywords:BPA  bisphenol A  2  2-bis(p-hydroxyphenyl)propane  BSA  bovine serum albumin  CMTC  cytoplasmic microtubule complex  CREST  calcinosis  Raynaud’s phenomenon  oesophagal motility abnormalities  sclerodactyly and telangiectasia  CYB  cytochalasin B  DAPI  4′  6′-diamidino-2-phenylindole  DES  diethylstilbestrol  E-3  4-bis(p-hydroxyphenyl)-hex-3-ene  DMBP  3  3′-dimethyl-BPA  DMSO  dimethylsulfoxide  E2  17β-estradiol  EDTA  ethylenediaminetetraacetate  sodium salt  EGTA  ethyleneglycolbis(2-aminoethylether)-N  N  N  N′-tetraacetic acid  FCS  fetal calf serum  FITC  fluoresceine isothiocyanate  MEM  minimal essential medium  MN  micronuclei  PBS-CMF  phosphate buffered saline  calcium- and magnesium-free  Pipes  piperazine-1  4-bis(2-ethanesulfonic acid)  R&  L  rings and loops  TMBP  3  5  3′  5′-tetramethyl-BPA
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