2,6-Di-tert-butylphenol and its quinone metabolite trigger aberrant transcriptional responses in C57BL/6 mice liver.

2,6-Di-tert-butylphenol (2,6-DTBP) is used as an antioxidant with wide commercial applications and its residues have been detected in various environmental matrices. 2,6-DTBP may enter human body via ingestion, inhalation or other exposure pathways. However, its susceptibility to biotransformation and potential of the metabolic products to trigger aberrant transcriptional responses remain unclear. Here, we investigated in vitro and in vivo biotransformation of 2,6-DTBP and characterized the RNA-Seq based transcriptional profiling of C57BL/6 mice liver after the exposure to 2,6-DTBP and its metabolites. 2,6-DTBP was metabolized into hydroxylated (2,6-DTBH) and para-quinone (2,6-DTBQ) products with residues detected in serum and liver of C57BL/6 mice. 2,6-DTBP and 2,6-DTBQ induced the aberrant transcription in C57BL/6 mice liver featured with 373-2861 differentially expressed genes (DEGs). They also up-regulated 1.09-2.92 fold mRNA expression of carcinogenesis-related genes such as Ccnd1, TGFβ1 and FOS in C57BL/6 mice liver. Our study indicated potential carcinogenic risk of 2,6-DTBP and its metabolites, beneficial to further evaluation of health risk of TBPs-related contaminants.