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, induced transcriptional activation in the yeast estrogen screen (YES) assay. They were potently oestrogenic in the mammalian based MVLN (transactivation) and E-SCREEN (proliferation) assays. This report on the transactivational, proliferative and genotoxic ability of the EDCs suggests that these chemicals may play a role in the etiology of male and female reproductive cancers.
Highlights
Screening for genotoxicity and proliferative ability of endocrine disrupting chemicals (EDCs) is a reliable tactic for the evaluation of genetic hazard and to obtaining information indicating possible carcinogenic potential
The results reported here for 4-OP, bisphenol A (BIS A), TOX, 2,4-D, GEN, COUM and EE2 in the ESCREEN assay suggest that they have the ability to mimic oestrogen action in breast cancer cells indicated here by proliferation and may act as promoters in the carcinogenic process by inducing proliferation and possibly permitting uncontrolled growth of spontaneous or carcinogen-induced mutations
The hypothesis that EDCs contribute to the decline in male and female reproductive health is supported by studies on wildlife and rodents
Summary
Screening for genotoxicity and proliferative ability of endocrine disrupting chemicals (EDCs) is a reliable tactic for the evaluation of genetic hazard and to obtaining information indicating possible carcinogenic potential. Oxidation of oestradiol forms catechol oestrogens which denote intermediates in the generation of more reactive semiquinones and quinones. These quinones can serve as substrates for redox cycling with the associated generation of reactive oxygen species which can bind covalently to peptides, proteins and DNA [1]. Most carcinogenic initiators are mutagenic or genotoxic and a battery of short-term in vitro mutagenicity and genotoxicity tests have been developed to allow the detection of chemicals with potential initiating activity. While modifications in cellular DNA are essential for carcinogenesis such perturbations alone are not sufficient to bring about cancer in all cases
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