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Forskningsartikel1987Vetenskapligt granskad

Uptake and Specific Binding of 2,3,7,8-Tetrachlorodibenzo-p-dioxin in the Olfactory Mucosa of Mice and Rats

Gillner, Mikael; Brittebo, Eva B.; Brandt, Ingvar; Söderkvist, Peter; Appelgren, Lars-Erik; Gustafsson, Jan-Åke


Whole-body autoradiography of mice and rats after i.v. administration of 2,3,7,8-[14C]tetrachlorodibenzo-p-dioxin ([14C]TCDD) showed a selective localization of radioactivity in the liver and nasal olfactory mucosa. In microautoradiograms of solvent extracted sections of the skulls of mice given injections of [3H]TCDD, no radioactivity was observed in the olfactory mucosa, suggesting that TCDD is not covalently bound in this tissue.

The amount of specific [3H]TCDD binding sites in cytosol from the ethmoturbinates of rats (33 fmol/mg cytosolic protein) was comparable to that of the liver cytosol as estimated by electrophoresis in polyacrylamide concentration gradient gel, and therefore probably too low to explain the retention of radioactivity in the olfactory mucosa. The specific TCDD binding species in the mucosa of the ethmoturbinates exhibited a similar binding affinity for [3H]TCDD, ligand specificity, and molecular weight as the TCDD receptor from rat liver. The 7-ethoxyresorufin O-deethylase activity of the mucosa of the ethmoturbinates was induced less than twice by administration of the TCDD receptor ligand β-naphthoflavone (5,6-benzoflavone) 40 h before killing. By administration of β-naphthoflavone (5,6-benzoflavone) 16 h before killing, mRNA coding for cytochrome P-450d but not for cytochrome P-450c was induced to detectable levels in the mucosa of the ethmoturbinal tissue of the rat.

The basal activity of 7-ethoxyresorufin O-deethylation of the mucosa of the ethmoturbinates of the rat was comparable to the corresponding activity of the liver. This basal metabolic activity of the ethmoturbinal tissue was only marginally inhibited by antibodies raised against β-naphthoflavone (5,6-benzoflavone) induced hepatic cytochrome P-450s. Thus, enzymes other than cytochrome P-450c may possibly account for a part of the basal 7-ethoxyresorufin O-deethylase activity in the rodent olfactory mucosa.

Publicerad i

Cancer Research
1987, Volym: 47, nummer: 15, sidor: 4150-4159

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    Cancer och onkologi

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