Molecular Endocrinology, Vol 7, 1596-1602, Copyright © 1993 by Endocrine Society

ARTICLES

Induction of c-fos and c-jun gene expression by phenolic antioxidants

HS Choi and DD Moore
Department of Molecular Biology, Massachusetts General Hospital, Boston 02114.

We have found that phenolic antioxidants specifically induce expression of the c-fos and c-jun protooncogenes. After treatment of quiescent human hepatoma HepG2 cells with butylated hydroxytoluene, butylated hydroxyanisole, or other phenolic antoxidants, the levels of c-fos and c-jun mRNAs are substantially increased. This response is antioxidant specific, dose dependent, and transient, with maximal levels at 3-6 h. The antioxidant-specific induction of c-fos/CAT promoter constructs in transient transfections indicates that at least a portion of this response is transcriptional. Deletions and point mutations map sequences required for the antioxidant response of the c-fos promoter to the serum response element. The antioxidant-specific induction of expression directed by a reporter plasmid containing four AP-1 sites and the induction of AP-1 DNA-binding activity confirm previous results indicating that antioxidant treatment increases AP-1 activity.

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