PT  - JOURNAL ARTICLE
AU  - Ram K. Sindhu
AU  - Masato Mitsuhashi
AU  - Yutaka Kikkawa
TI  - Induction of Cytochrome P-450 1A2 by Oxidized Tryptophan in Hepa lclc7 Cells
DP  - 2000 Mar 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 1008--1014
VI  - 292
IP  - 3
4099  - http://jpet.aspetjournals.org/content/292/3/1008.short
4100  - http://jpet.aspetjournals.org/content/292/3/1008.full
SO  - J Pharmacol Exp Ther2000 Mar 01; 292
AB  - Recent studies from this laboratory have demonstrated thatl-tryptophan, after oxidation either by UV-irradiation or ozone, induces aryl hydrocarbon receptor (AhR) activation and binding of the liganded AhR complex to its specific DNA recognition site, thereby initiating transcription of the cytochrome P-450 1a1 (Cyp1a1) gene with concomitant increase of CYP1A1 protein and 7-ethoxyresorufin O-deethylase activity in wild-type mouse hepatoma cells, Hepa lclc7 (Hepa-1), in culture. Temporary inhibition of protein synthesis by cycloheximide resulted in superinduction of oxidized tryptophan-inducible CYP1A1 mRNA, protein, and 7-ethoxyresorufin O-deethylase activity in Hepa-1 cells. In the present communication, the results obtained by immunoblot analyses with monoclonal CYP1A1/1A2 antibody (NIH 1-7-1) demonstrate that both UV- or ozone-oxidized tryptophan also induce CYP1A2 protein in Hepa-1 cells. CYP1A2 mRNA, detected by reverse transcription-polymerase chain reaction, was markedly induced in the UV- or ozone-oxidized tryptophan-treated cells. Temporary inhibition of protein synthesis by cycloheximide further induced oxidized tryptophan-inducible CYP1A2 mRNA as well as the protein in Hepa-1 cells. This is the first report demonstrating the induction of CYP1A2 mRNA and protein in Hepa-1 cells. The American Society for Pharmacology and Experimental Therapeutics