screening for genotoxicity and oestrogenicity of endocrine disrupting chemicals in vitro筛查基因毒性和内分泌干扰化学物质的oestrogenicity体外.pdf

Journal of Environmental Protection, 2012, 3, 902-914 /10.4236/jep.2012.328105 Published Online August 2012 (http://www.SciRP.org/journal/jep) Screening for Genotoxicity and Oestrogenicity of Endocrine Disrupting Chemicals in Vitro * Karthryn M. Quinn-Hosey, James J. Roche, Andrew M. Fogarty, Concepta A. Brougham Endocrine Disruption Group, Department of Life and Physical Sciences, School of Science, Athlone Institute of Technology, Athlone, Co. Westmeath, Ireland. * Email: cbrougham@ait.ie Received May 16th, 2012; revised June 18th, 2012; accepted July 20th, 2012 ABSTRACT A diverse range of endocrine disrupting chemicals (EDCs) was examined, using an in vitro test system, for critical events required for the onset of carcinogenesis in vivo. The initiation stage of carcinogenesis is a genotoxic process. 4-Octylphenol (alkylphenol), bisphenol A (plasticiser), coumestrol and genistein (phytoestrogens), 2,4-dichlorophe- noxyacetic acid and toxaphene (pesticides) and ethinylestradiol (synthetic hormone) were investigated for potential mutagencicity, DNA strand breakage, clastogenicity and DNA repair. Significant induction in the percentage of cells containing micronuclei was observed for all the EDCs. Toxaphene and coumestrol were mutagenic in the Ames assay. They also induced significant levels of unscheduled DNA synthesis and DNA strand breakage. Bisphenol A induced low level DNA strand breakage in HepG2 cells in the comet assay. The EDCs, with the exception of toxaphene, in- duced transcriptional activation in the yeast estrogen screen (YES) assay. They were potently oestrogenic in the mam- malian based MVLN (transactivation) and E-SCREEN (proliferation) assays. This report on the transactivational, pro- liferative and genotoxic ability o