Effects of the organochlorine p,p’-DDT on MCF-7 cells: investigating metabolic and immune modulatory transcriptomic changes

Abstract

The organochlorine pesticide dichloro-diphenyl-trichloroethane (DDT) is persistent in the environment and leadsto adverse human health effects. High levels in breast milk pose a threat to both breast tissue and nursing infants.The objectives of this study were to investigate DDT-induced transcriptomic alterations in enzymes and trans-porters involved in xenobiotic metabolism, immune responses, oxidative stress markers, and cell growth in ahuman breast cancer cell line. MCF-7 cells were exposed to both environmentally-relevant and previously-testedconcentrations ofp,p’-DDT in a short-term experiment. Significant up-regulation of metabolizing enzymes andtransporters (ACHE,GSTO1,NQO1andABCC2) and oxidative stress markers (CXCL8,HMOX-1,NFE2L2andTNF) was clearly observed. Conversely,UGT1A6,AHRand cell growth genes (FGF2andVEGFA) were severelydown-regulated. Identification of these genes helps to identify mechanisms ofp,p’-DDT action within cells andmay be considered as useful biomarkers for exposure to DDT contamination