Mutagenicity of bisphenol A and its suppression by interferon-alpha in human RSa cells

Bisphenol A is used as a monomer in the production of polycarbonate plastic products. The widespread use of bisphenol A has raised concerns about its effects in humans. Since there is little information on the mutagenic poten tial of the chemical, the mutagenicity of bisphenol A was tested using huma n RSa cells, which has been utilized for identification of novel mutagens. In genomic DNA from cells treated with bisphenol A at concentrations rangin g from 1 x 10(-7) to 1 x 10(-5) M, base substitution mutations at K-ras cod on 12 were detected using PCR and differential dot-blot hybridization with mutant probes. Mutations were also detected using the method of peptide nuc leic acid (PNA)-mediated PCR clamping. The latter method enabled us to dete ct the mutation in bisphenol A-treated cells at a dose (1 x 10(-8) M) equiv alent to that typically found in the environment Induction of ouabain-resis tant (Oua(R)) phenotypic mutation was also found in cells treated with 1 x 10(-7) and 1 x 10(-5) M of bisphenol A. The induction of K-ms codon 12 muta tions and OuaR mutations was suppressed by pretreating RSa cells with human interferon (HuIFN)-alpha prior to bisphenol A treatment. The cells treated with bisphenol A at the concentration of 1 x 10(-6) M elicited unscheduled DNA synthesis (UDS). These findings suggested that bisphenol A has mutagen icity in RSa cells as well as mutagens that have been tested in these cells , and furthermore, that a combination of the PNA-mediated PCR clamping meth od with the human RSa cell line may be used as an assay system for screenin g the mutagenic chemicals at very low doses. (C) 2001 Elsevier Science B.V. All rights reserved.