Genotoxic potentials and related mechanisms of bisphenol A and other bisphenol compounds: A comparison study employing chicken DT40 cells

• Published in: Chemosphere (Oxford) 2013-09, Vol.93 (2), p.434-440
• Main Authors: Lee, Sangwoo, Liu, Xiaoshan, Takeda, Shunichi, Choi, Kyungho
• Format: Article
• Language: English
• Subjects: Animals; Benzhydryl Compounds - toxicity; Biological and medical sciences; bisphenol A; carcinogenesis; Cell Line; Cell Proliferation - drug effects; Chemical and industrial products toxicology. Toxic occupational diseases; Chemical mutagenesis; Chickens; chromosome aberrations; Chromosome Aberrations - drug effects; containers; cytotoxicity; DNA damage; DNA repair; Double strand break; DT40 cell; genotoxicity; Homologous recombination; Medical sciences; Models, Molecular; Mutagenicity Tests - methods; Mutagens - toxicity; mutants; Nucleic Acid Conformation; Phenols - toxicity; plastics; Polycarbonate; RAD54; reproduction; Toxicology; toys; Various organic compounds
• ISSN: 0045-6535; 1879-1298
• DOI: 10.1016/j.chemosphere.2013.05.029

[Display omitted] •Bisphenol A and alternative bisphenols showed genotoxic potentials in DT40 cells.•Their mechanisms involve double strand breaks rescued by homologous recombination.•RAD54−/− DT40 mutant cells were the most hypersensitive to most bisphenols.•Genotoxic potential was confirmed by chromosomal aberration and γ-H2AX foci. Bisphenol A (BPA) has been found in plastic food containers, paper currencies and toys. BPA has been reported for various adverse health concerns including reproduction, development and carcinogenesis. These potential health implications have led to increasing use of alternative bisphenols such as bisphenol F and bisphenol S among many. However, little is known about the toxicity of alternative bisphenols and most of the toxicological information is limited to endocrine disrupting potentials. In this study, we evaluated cytotoxicity and the genotoxic potentials of several bisphenol compounds, and identified the mechanism of genotoxicity using a panel of mutant chicken DT40 cell lines deficient in DNA repair pathways. Several bisphenols including bisphenol AP, bisphenol M, or bisphenol P exerted genotoxic potentials that are greater than that of BPA. Generally RAD54−/− mutant cells were the most sensitive to all bisphenols except for bisphenol F, suggesting the induction of DNA double-strand breaks that could be rescued by homologous recombination. Genotoxic potential of bisphenols was confirmed by chromosomal aberration assay and γ-H2AX foci forming assay between wild-type and RAD54−/− mutant. Among the tested bisphenols, BPP at 12.5μM showed the greatest genotoxic potency, inducing chromosomal aberration and γ-H2AX foci in RAD54−/− mutant by 2.6 and 4.8 folds greater than those in wild-type, respectively. Our results clearly show several alternative bisphenols can cause genotoxicity that could be rescued by homologous recombination pathway, and some bisphenols induced even greater genotoxic potentials than that of BPA.