Bisphenol A modulation of DNA repair

To better understand gene expression changes that occur after BPA co-exposure with the oxidizing agent potassium bromate (KBrO3), we have employed whole genome microarray expression profiling to identify genes that are uniquely regulated by exposure to KBrO3, BPA, and co-exposure to both agents. Mouse embryonic fibroblasts deficient in the non-homologous end joining protein Ku70 were exposed to KBrO3, BPA, and both KBrO3 and BPA. Treated samples were isolated 4 and 24 hours after the initiation of DNA damage, along with control untreated samples. Gene expression changes were identified between the treated samples and the controls. From these comparisons, 755 unique gene changes were attributed only to the co-exposure condition at both time points, with only 86 of these genes overlapping between 4 and 24 h. The 24 h time point showed significant up-regulation of DNA repair genes that address oxidatively-induced DNA damage, including Ercc4, Ercc5, Ercc8, and Ogg1. Mouse embryonic fibroblasts deficient in the non-homologous end joining protein Ku70 were exposed as follows: KBrO3 only samples were exposed to 20 mM KBrO3 for 1 hour, then allowed to repair for an additional 3 or 23 hours; BPA only samples were exposed to 150 uM BPA for 4 or 24 hours; and co-exposed samples were exposed to 150 uM BPA for 1 h, then 20 mM KBrO3 and 150 uM BPA for 1 h, and finally, 150 uM BPA for an additional 3 or 23 hours. Treated samples were isolated 4 and 24 hours after the initiation of DNA damage, along with control untreated samples at the same time points. Three independent experiments were performed at each time (4 or 24 hours).