Induction of cytochrome P4501A1 by ozone-oxidized tryptophan in Hepa lclc7 cells.
The present investigation was undertaken to determine whether administration of O3-oxidized amino acids to mouse hepatoma cells, Hepa lclc7 (Hepa-1), in culture would effect Cyp1a1 gene expression. The results demonstrate that, of all the amino acids tested, only O3-oxidized tryptophan caused a significant induction of CYP1A1-dependent 7-ethoxyresorufin O-deethylase (EROD) activity compared to the controls (p < 0.01). CYP1A1 mRNA and protein were markedly induced in the O3-oxidized tryptophan administered group compared to the controls. Gel mobility shift assays using nuclear extracts of Hepa-1 cells revealed that oxidized products of tryptophan can induce both aryl hydrocarbon receptor (AhR) transformation and binding of the liganded AhR complex to its specific DNA recognition site, thereby initiating transcription of the Cyp1a1 gene with concomitant increase of CYP1A1 protein and EROD activity in Hepa-1 cells.
Sindhu
R K
RK
Department of Pathology and Community & Environmental Medicine, College of Medicine, University of California at Irvine 92697-4800, USA. rksindhu@uci.edu
Rasmussen
R E
RE
Kikkawa
Y
Y
D000818:Animals; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis / Q000235:genetics*; D004790:Enzyme Induction / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D008114:Liver Neoplasms, Experimental; D051379:Mice; D010084:Oxidation-Reduction; D010126:Ozone / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D018336:Receptors, Aryl Hydrocarbon / Q000502:physiology; D014158:Transcription, Genetic / Q000187:drug effects; D014364:Tryptophan / Q000031:analogs & derivatives* / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon; D010126:Ozone; D014364:Tryptophan; D019363:Cytochrome P-450 CYP1A1