title: AhR-agonistic, anti-androgenic, and anti-estrogenic potencies of 2-isopropylthioxanthone (ITX) as determined by in vitro bioassays and gene expression profiling.
abstract: 2-Isopropylthioxanthone (2-ITX) has been widely used as a photoinitiator in printing ink of packaging materials. A few years ago, this compound got special attention since it was detected in milk and fruit drinks. Since little is known about possible effects of this compound on human health, studies were initiated to investigate its properties, starting with in vitro studies. Structural similarities between ITX and the AhR-agonists 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and furanocoumarins, prompted us to investigate whether ITX could have the potency to activate the AhR. ITX showed a clear response in the DR CALUX bioassay and also induced EROD activity in H4IIE rat hepatoma cells. Microarray studies in these cells showed a gene expression profile similar to that of TCDD. Moreover, using yeast-based estrogen and androgen bioassays, it was demonstrated that ITX, but not TCDD, has potential anti-estrogenic and anti-androgenic properties. The observed in vitro effects warrant further in vivo studies for confirmation and hazard characterization.
authors.affiliation: RIKILT-Institute of Food Safety, Wageningen UR, Wageningen, The Netherlands. ad.peijnenburg@wur.nl
authors.forename: Ad
authors.initials: A
authors.lastname: Peijnenburg
authors.forename: Jenneke
authors.initials: J
authors.lastname: Riethof-Poortman
authors.forename: Hakan
authors.initials: H
authors.lastname: Baykus
authors.forename: Liza
authors.initials: L
authors.lastname: Portier
authors.forename: Toine
authors.initials: T
authors.lastname: Bovee
authors.forename: Ron
authors.initials: R
authors.lastname: Hoogenboom
mesh_terms: D000726:Androgen Antagonists / Q000633:toxicity; D000818:Animals; D015374:Biosensing Techniques; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis; D052244:Endocrine Disruptors / Q000633:toxicity*; D020847:Estrogen Receptor Modulators / Q000633:toxicity; D015870:Gene Expression / Q000187:drug effects*; D020869:Gene Expression Profiling; D022781:Hepatocytes / Q000187:drug effects* / Q000201:enzymology; D006727:Hormone Antagonists / Q000633:toxicity*; D008156:Luciferases / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D018336:Receptors, Aryl Hydrocarbon / Q000037:antagonists & inhibitors / Q000187:drug effects*; D012441:Saccharomyces cerevisiae / Q000187:drug effects; D013892:Thioxanthenes / Q000633:toxicity*
chemical_list: D000726:Androgen Antagonists; D052244:Endocrine Disruptors; D020847:Estrogen Receptor Modulators; D006727:Hormone Antagonists; D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon; D013892:Thioxanthenes; C518329:isopropyl-9H-thioxanthen-9-one; D008156:Luciferases; D019363:Cytochrome P-450 CYP1A1