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Microarray analysis of gene expression in peripheral blood mononuclear cells from dioxin-exposed human subjects
- Publication Year :
- 2007
-
Abstract
- Tetrachlorodibenzo-p-dioxin (TCDD) is classified as a human carcinogen and exerts toxic effects on the skin (chloracne). Effects on reproductive, immunological, and endocrine systems have also been observed in animal models. TCDD acts through the aryl hydrocarbon receptor (AhR) pathway influencing largely unknown gene networks. An industrial accident in Seveso, Italy in 1976 exposed thousands of people to substantial quantities of TCDD. Twenty years after the exposure, this study examines global gene expression in the mononuclear cells of 26 Seveso female never smokers, with similar age, alcohol consumption, use of medications, and background plasma levels of 22 dioxin congeners unrelated to the Seveso accident. Plasma dioxin levels were still elevated in the exposed subjects. We performed analyses in two different comparison groups. The first included high-exposed study subjects compared with individuals with background TCDD levels (average plasma levels 99.4 and 6.7ppt, respectively); the second compared subjects who developed chloracne after the accident, and those who did not develop this disease. Overall, we observed a modest alteration of gene expression based on dioxin levels or on chloracne status. In the comparison between high levels and background levels of TCDD, four histone genes were up-regulated and modified expression of HIST1H3H was confirmed by real-time PCR. In the comparison between chloracne case-control subjects, five hemoglobin genes were up-regulated. Pathway analysis revealed two major networks for each comparison, involving cell proliferation, apoptosis, immunological and hematological disease, and other pathways. Further examination of the role of these genes in dioxin induced-toxicity is warranted.
- Subjects :
- Adult
medicine.medical_specialty
Polychlorinated Dibenzodioxins
Microarray
Gene Expression
Apoptosis
Biology
Toxicology
Peripheral blood mononuclear cell
Histones
Hemoglobins
Acneiform Eruptions
Internal medicine
Gene expression
medicine
Settore MED/44 - Medicina del Lavoro
Humans
Carcinogen
Cell Proliferation
Glutathione Transferase
Oligonucleotide Array Sequence Analysis
Reverse Transcriptase Polymerase Chain Reaction
Microarray analysis techniques
Gene Expression Profiling
Computational Biology
Environmental Exposure
Middle Aged
Aryl hydrocarbon receptor
medicine.disease
Gene expression profiling
Chloracne
Endocrinology
Italy
Leukocytes, Mononuclear
biology.protein
Environmental Pollutants
Female
Biomarkers
Blood
Leukemia
Tetrachlorodibenzo-p-dioxin (TCDD)
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....1747ecb29d5fbc3ebd3a79fe8b901d9b