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 n umerous consumer products. The release of BP-A from some of these mate rials has recently been reported. BP-A is a weak estrogen and structur ally related to the aneuploidogenic stilbene estrogen diethylstilbestr ol (DES). We have therefore studied BP-A and four other bisphenols for their aneuploidogenic potential by assaying their (i) interference wi th the cell-free assembly of microtubules (NIT); (ii) disruption of th e 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 co ncentrations without gross cytotoxicity, BP-A as well as its alkyl-flu orinated and ring-methylated analog were active at all endpoints teste d, whereas the bisphenol without alkyl groups was completely inactive. 4,4'-Dihydroxybenzophenone was inactive against cell-free and cytopla smic 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 induc ed MN were CREST-positive, implying that they contain whole chromosome s/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.