Characterization of serum-induced CYP1A1 expression and activity in mouse embryo fibroblasts

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The AhR is a ligand-activated transcription factor that mediates the toxic effects of environmental contaminants that include TCDD. Using a TCDD dose-response treatment in MEFs, we observed a super induction of CYP1A1 with newborn calf serum (NCS) in the presence (10nM/15nM) of TCDD. In addition to NCS, fetal bovine serum (FBS) also has the capability to yield a CYP1A1 super induction. These results suggest that components within the sera affect the activity of the AhR and consequent CYP1A1 expression. To pursue this idea, characterization of the serum factors were investigated. The findings indicated that serum factor(s) in both sera are heat sensitive at 50◦C, withstand removal from charcoal stripping sera and are ¡Ý 10,000 kDa in size. Using RT-PCR, we found that NCS factors only, could super induce CYP1A1 at the gene level. Moreover, MEFs are the only cells observed in this study that are susceptible to CYP1A1 super induction.

TCDD, serum, CYP1A1, AHR