[Why is dioxin harmful?].
The scandal in Belgium last spring has drawn attention to the environmental hazards of dioxins. Previous production of pesticides and widespread combustion of organic material in the presence of chloride have lead to environmental accumulation of these toxicants, which more precisely are termed polychlorinated dibenzo-p-dioxins and dibenzofurans. Their very long biological half-lives in combination with detectable biological effects at very low concentrations have caused health concerns. Chloracne is the only well documented health effect in man, but there are experimental evidence for carcinogenic, teratogenic, reproductive and immunosuppressive effects. In this presentation we review current knowledge about the cellular effects of dioxins. Dioxins bind to and exert their effects through the cytoplasmic aryl hydrocarbon receptor, which acts as a transcription factor and regulates a number of cytokines and microsomal enzymes. Furthermore, dioxins interfere with hormonal signalling, and anti-oestrogenic effects, vitamin A inhibition and thyroxin mimicry have been reported. Recently, effects on intracellular growth factor signalling have been demonstrated. Dioxins inhibit epidermal growth factor receptor, activate protein kinase C and other intracellular signal transducers, and activate transcription factors. As overall understanding of their cellular mechanisms of toxicity is lacking, we do not possess a complete basis for estimating the adverse health effects of this group of environmental toxicants.
Huitfeldt
H S
HS
Laboratorium for toksikopatologi, Universitetet i Oslo.
Lindeman
B
B
Skarpen
E
E
Oksvold
M P
MP
Wierød
L
L
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001572:Benzofurans / Q000009:adverse effects / Q000737:chemistry / Q000506:poisoning / Q000633:toxicity; D002273:Carcinogens; D004147:Dioxins / Q000009:adverse effects* / Q000737:chemistry / Q000506:poisoning / Q000633:toxicity; D004785:Environmental Pollutants / Q000009:adverse effects* / Q000506:poisoning / Q000633:toxicity; D006728:Hormones / Q000378:metabolism; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000737:chemistry / Q000506:poisoning / Q000633:toxicity; D000072317:Polychlorinated Dibenzodioxins / Q000009:adverse effects* / Q000737:chemistry / Q000506:poisoning / Q000633:toxicity; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism; D012098:Reproduction / Q000187:drug effects; D012307:Risk Factors; D013723:Teratogens
D001572:Benzofurans; D002273:Carcinogens; D004147:Dioxins; D004785:Environmental Pollutants; D006728:Hormones; D007166:Immunosuppressive Agents; D000072317:Polychlorinated Dibenzodioxins; D011956:Receptors, Cell Surface; D013723:Teratogens