Examination of gene expression changes after exposure to 29 chemicals in rat primary hepatocytes

In this study we examined transcriptional responses to 29 ToxCast chemicals in dose-response format. The chemicals were selected because in vitro transcriptional effects could be extrapolated to in vivo effects including liver cancer and steatosis incidences using in vitro to in vivo extrapolation. Overall design: Rat primary hepatocytes were plated on collagen-coated plates and treated with DMSO (0.1%) or 6 concentrations of chemical (100 or 33.3 uM as the top concentration with a log2 step-down of dose level). Cells were treated for 24 hrs. Purified RNA was examined for gene expression changes using the rat TempO-Seq targeted RNA-Seq platform (BioSpyder, Inc; Carlsbad CA). The following chemicals were examined in dose-response format: Acetochlor, Alachlor, Ametryn, Bensulide, Bisphenol A, Carbaryl, Cyclanilide, Cyproconazole, Cyprodinil, Di-2-ethylhexyl phthalate, Dichlobenil, Dimethenamid, Dithiopyr, Etoxazole, Fludioxonil, Flusilazole, Hexaconazole, Imazalil, Isoxaflutole, Oxadiazon, Perfluorooctanoic acid, Perfluorooctanesulfonate, S-Bioallethrin, Simazine, Tetraconazole, Triadimefon, Triclosan, Triflumizole, Triticonazole. In addition, a number of reference chemicals were examined at one concentration (17beta-estradiol, Dexamethasone, GW4046, Oltipraz, Pregnenolone 16-alpha-carbonitrile, Sulforaphane, TCPOBOP, Testosterone, WY-14,643).