Interference with microtubules and induction of micronuclei in vitro by various bisphenols

Bisphenols, in particular bisphenol-A (BP-A), are monomers of various plastics including polycarbonates and epoxy resins which are used in numerous consumer products. The release of BP-A from some of these materials has recently been reported. BP-A is a weak estrogen and structurally related to the aneuploidogenic stilbene estrogen diethylstilbestrol (DES). We have therefore studied BP-A and four other bisphenols for their aneuploidogenic potential by assaying their (i) interference with the cell-free assembly of microtubules (NIT); (ii) disruption of the cytoplasmic MT complex in cultured Chinese hamster V79 cells: (iii) disruption of the mitotic spindle and induction of metaphase arrest in V79 cells; and (iv) induction of micronuclei (MN) in V79 cells. At concentrations without gross cytotoxicity, BP-A as well as its alkyl-fluorinated and ring-methylated analog were active at all endpoints tested, whereas the bisphenol without alkyl groups was completely inactive. 4,4'-Dihydroxybenzophenone was inactive against cell-free and cytoplasmic MT but disrupted the mitotic spindle and induced metaphase arrest and MN. The MN caused by the various bisphenols were analyzed for the presence of kinetochores by staining with CREST antibodies. All induced MN were CREST-positive, implying that they contain whole chromosomes/chromatids. The effects on MT and the induction of metaphase arrest and of CREST-positive MN suggest that the environmental estrogen BP-A and some of its analogs are potential aneuploidogens.