UV-induced CYP1A1 gene expression in human cells is mediated by tryptophan.
Induction of cytochrome P-4501A1 (CYP1A1) activity by UV has been observed earlier in animal studies via a mechanism that has not yet been resolved. Our previous data have indicated that formylated indolocarbazoles which are formed by UV irradiation of tryptophan solutions are very potent Ah-receptor agonists. To evaluate the effect of UV light on cytochrome P4501A1 gene expression, we studied the induction of CYP1A1 mRNA by UV irradiation of cultured human keratinocytes (HaCaT cell line), primary human blood lymphocytes and mouse Hepa-1 cells. The cells were exposed to UV light delivered by a bank of 6 Philips TL20/12RS sun lamps emitting primarily in the UVB range in the absence and presence of tryptophan. A semiquantitative reverse transcriptase-linked polymerase chain reaction (RT-PCR) was used for analysis of gene expression in the treated cells. The results show that the CYP1A1 mRNA level induced by UV in the presence of tryptophan was higher than that induced by UV alone in both HaCaT cells and lymphocytes after 3 h of incubation post-UV irradiation. To find out if the induction by UV light is caused by the formation of an Ah receptor ligand, Hepa-1 wild-type and Ah receptor deficient c12 cell lines were applied. Wild-type (wt) cells were inducible either by the tryptophan photoproduct 6-formylindolo[3,2-b]carbazole (FICZ) or by UV-irradiation but very low or undetectable levels were observed in the c12 cells. This shows that the induction of gene expression by FICZ and UV is Ah receptor dependent. Together, these results indicate that UV-induced CYP1A1 gene expression in mammalian cells is mediated by an Ah receptor ligand formed from tryptophan. Thus, the photoproducts of tryptophan are suggested to be mediators of light via binding to the Ah receptor and as such also could have a role in light-regulated biological rhythms.
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Karolinska Institutet, Department of Genetic and Cellular Toxicology, Stockholm University, Sweden.
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D000818:Animals; D002227:Carbazoles / Q000494:pharmacology; D002460:Cell Line; D002478:Cells, Cultured; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis* / Q000235:genetics; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D015603:Keratinocytes / Q000187:drug effects / Q000528:radiation effects; D008214:Lymphocytes / Q000187:drug effects / Q000528:radiation effects*; D051379:Mice; D015394:Molecular Structure; D012333:RNA, Messenger / Q000378:metabolism; D018336:Receptors, Aryl Hydrocarbon / Q000819:agonists / Q000378:metabolism; D014364:Tryptophan / Q000494:pharmacology* / Q000528:radiation effects; D014466:Ultraviolet Rays
C111855:6-formylindolo(3,2-b)carbazole; D002227:Carbazoles; D004791:Enzyme Inhibitors; D007211:Indoles; D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon; D014364:Tryptophan; D019363:Cytochrome P-450 CYP1A1