Identification of a novel dioxin-inducible cytochrome P450.
Representational difference analysis was used to isolate cDNAs corresponding to 2,3,7,8-tetrachlorodibenzo-p-dioxin (dioxin)-inducible genes from mouse Hepa-1 cells. One cDNA encoded a novel cytochrome P450. The human homolog was also isolated and later proved to be human CYP2S1. The induction of mouse CYP2S1 mRNA by dioxin represents a primary response and required the aryl hydrocarbon receptor and aryl hydrocarbon receptor nuclear translocator proteins. The induction of CYP2S1 also occurred in mouse liver and lung, with the highest expression found in lung. CYP2S1 was also inducible in a human lung epithelial cell line. The dioxin-inducibility of CY2S1 is exceptional, because all previously well-characterized cases of the induction of cytochromes P450 by dioxin involve members of the CYP1 family.
Rivera
Steven P
SP
Department of Pathology and Laboratory Medicine, Jonsson Comprehensive Cancer Center, and Molecular Biology Institute, UCLA, Los Angeles, California, USA.
Saarikoski
Sirkku T
ST
Hankinson
Oliver
O
D000595:Amino Acid Sequence; D000818:Animals; D002273:Carcinogens / Q000494:pharmacology*; D002471:Cell Transformation, Neoplastic; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000187:drug effects / Q000235:genetics; D004147:Dioxins / Q000494:pharmacology*; D004790:Enzyme Induction / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D010105:Oxygenases / Q000096:biosynthesis* / Q000187:drug effects / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000187:drug effects; D017386:Sequence Homology, Amino Acid; D014162:Transfection; D014407:Tumor Cells, Cultured
D002273:Carcinogens; D004147:Dioxins; D012333:RNA, Messenger; D003577:Cytochrome P-450 Enzyme System; D010105:Oxygenases; C422564:CYP2S1 protein, human