title: Dioxin exposure of human CD34+ hemopoietic cells induces gene expression modulation that recapitulates its in vivo clinical and biological effects.
abstract: 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) has a large number of biological effects, including skin, cardiovascular, neurologic diseases, diabetes, infertility, cancers and immunotoxicity. We analysed the in vitro TCDD effects on human CD34+ cells and tested the gene expression modulation by means of microarray analyses before and after TCDD exposure. We identified 257 differentially modulated probe sets, identifying 221 well characterized genes. A large part of these resulted associated to cell adhesion and/or angiogenesis and to transcription regulation. Synaptic transmission and visual perception functions, with the particular involvement of the GABAergic pathway were also significantly modulated. Numerous transcripts involved in cell cycle or cell proliferation, immune response, signal transduction, ion channel activity or calcium ion binding, tissue development and differentiation, female or male fertility or in several metabolic pathways were also affected after dioxin exposure. The transcriptional profile induced by TCDD treatment on human CD34+ cells strikingly reproduces the clinical and biological effects observed in individuals exposed to dioxin and in biological experimental systems. Our data support a role of dioxin in the neoplastic transformation of hemopoietic stem cells and in immune modulation processes after in vivo exposure, as indicated by the epidemiologic data in dioxin accidentally exposed populations, providing a molecular basis for it. In addition, TCDD alters genes associated to glucidic and lipidic metabolisms, to GABAergic transmission or involved in male and female fertility, thus providing a possible explanation of the diabetogenic, dyslipidemic, neurologic and fertility effects induced by TCDD in vivo exposure.
authors.affiliation: UO Ematologia 1-Centro Trapianti di Midollo, Milan, Italy. n.fracchiolla@policlinico.mi.it
authors.forename: Nicola Stefano
authors.initials: NS
authors.lastname: Fracchiolla
authors.forename: Katia
authors.initials: K
authors.lastname: Todoerti
authors.forename: Pier Alberto
authors.initials: PA
authors.lastname: Bertazzi
authors.forename: Federica
authors.initials: F
authors.lastname: Servida
authors.forename: Paolo
authors.initials: P
authors.lastname: Corradini
authors.forename: Cristiana
authors.initials: C
authors.lastname: Carniti
authors.forename: Antonio
authors.initials: A
authors.lastname: Colombi
authors.forename: Angela
authors.initials: A
authors.lastname: Cecilia Pesatori
authors.forename: Antonino
authors.initials: A
authors.lastname: Neri
authors.forename: Giorgio Lambertenghi
authors.initials: GL
authors.lastname: Deliliers
mesh_terms: D018952:Antigens, CD34 / Q000096:biosynthesis*; D004785:Environmental Pollutants / Q000494:pharmacology*; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects*; D006412:Hematopoietic Stem Cells / Q000187:drug effects* / Q000502:physiology; D006413:Hematopoietic System / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D012313:RNA / Q000737:chemistry / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D018952:Antigens, CD34; D004785:Environmental Pollutants; D000072317:Polychlorinated Dibenzodioxins; D012313:RNA