BISPHENOL-A INDUCES CELLULAR-TRANSFORMATION, ANEUPLOIDY AND DNA ADDUCT FORMATION IN CULTURED SYRIAN-HAMSTER EMBRYO CELLS

Bisphenol-A (BP-A) is a major component of epoxy, polycarbonate and ot her resins. For an assessment of in vitro carcinogenicity and related activity of BP-A, the abilities of this compound to induce cellular tr ansformation and genetic effects were examined simultaneously using th e Syrian hamster embryo (SHE) cell model. Cellular growth was reduced by continuous treatment with BP-A at doses greater than or equal to 10 0 mu M. However, colony-forming efficiencies were not decreased signif icantly following treatment with up to 200 mu M BP-A for 48 hr. Morpho logical transformation of SHE cells was induced by treatment of cells with BP-A at 50 to 200 mu M for 48 hr. BP-A exhibited transforming act ivity at doses greater than or equal to 50 mu M but was less active th an the benzo[a]pyrene used as a positive control. Over the dose range that resulted in cellular transformation, treatment of SHE cells with BP-A failed to induce gene mutations at the Na+/K+ ATPase locus or the hprt locus. No statistically significant numbers of chromosomal aberr ations were detected in SHE cells treated with BP-A. However, treatmen t of cells with BP-A induced numerical chromosomal changes in the near diploid range at doses that induced cellular transformation. P-32-Pos tlabeling analysis revealed that exposure of cells to BP-A also elicit ed DNA adduct formation in a dose-dependent fashion. Our results indic ate that BP-A has cell-transforming and genotoxic activities in cultur ed mammalian cells and potential carcinogenic activity. (C) 1998 Wiley -Liss, Inc.