Cytotoxic effects of BADGE (bisphenol A diglycidyl ether) and BFDGE (bisphenol F diglycidyl ether) on Caco-2 cells in vitro

Bisphenol A diglycidyl ether (BADGE) and bisphenol F diglycidyl ether (BFDGE) are used as starting substances for the manufacturing of epoxy resins used in internal can coatings. They are obtained by a condensation reaction between epichlorohydrin with bisphenol A and bisphenol F, respectively. These potential endocrine disrupting chemicals are able to enter the food chain and to reach the intestinal epithelium, causing structural and functional damages. The human colorectal adenocarcinoma cell line Caco-2 is a widely used in vitro model of the intestinal cells. The aim of this study was to characterize BADGE and BFDGE toxicity in Caco-2 cells, in particular, at the cellular and molecular level. Using several approaches, we characterized BADGE- and BFDGE-induced cell toxicity in Caco-2 cells. The treatment was done using different concentrations up to cytotoxic doses and different times of exposure to the agents. We evaluated the effect of these compounds on cell morphology, cell detachment, cell proliferation, F-actin disruption and plasma membrane integrity. Both compounds are able to induce morphological changes, cell detachment from the substratum and to inhibit cell proliferation, being these effects time and dose-dependent. Moreover, BADGE and BFDGE induce F-actin depolymerization, this effect is very potent at 24 h of incubation with the agents and a complete F-actin disruption can be observed at 200 μM BADGE or BFDGE. In addition, cell integrity is not damaged, since neither propidium iodide uptake nor LDH release takes place in Caco-2 cells exposed to high doses of these agents for 24 h.