The distribution of [14C]-2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and its effect on the vitamin A content in parenchymal and stellate cells of rat liver.
Isolated liver cells from male Sprague-Dawley rats given a single dose of [14C]-2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; 10 micrograms, 0.9 microCi/kg body wt in corn oil, p.o.) or vehicle only were separated into parenchymal and nonparenchymal cell fractions 4 h, and 1, 4, 7, 25, 50, and 147 d after treatment. Vitamin A content and TCDD-derived radioactivity were estimated in the parenchymal cells and in the stellate cells, which were identified and quantified in these fractions. Similar levels of vitamin A (0.3 +/- 0.4 nmol per million cells or 0.5 +/- 0.7 mumol per liver; values are mean +/- SD for 56 rats) were found in parenchymal cells from both control and TCDD-treated rats. However, while the vitamin A content of stellate cells increased from 14 to 46 nmol per million cells (i.e., from 1.7 to 7.7 mumol per liver) in control rats over the course of the study, stellate cells from TCDD-exposed rats showed no increase in vitamin A level until at least 25 d after exposure and remained at a level about 30% below the controls thereafter. TCDD-derived radioactivity resided mainly in the parenchymal cell compartment, although stellate cells contained more radioactivity per cell. Most of the radioactivity in parenchymal cells was eliminated with a half-life of 13 d, whereas the remainder persisted with an elimination half-life of 70 d. The elimination half-life in stellate cells was estimated to be 52 d. Thus, TCDD inhibited storage of vitamin A in stellate cells until 60-90% of the TCDD-derived radioactivity had been eliminated from the liver.
Håkansson
H
H
Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Hanberg
A
A
D000818:Animals; D002250:Carbon Radioisotopes; D002469:Cell Separation; D004147:Dioxins / Q000493:pharmacokinetics*; D006207:Half-Life; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D000072317:Polychlorinated Dibenzodioxins / Q000493:pharmacokinetics* / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014018:Tissue Distribution; D014801:Vitamin A / Q000378:metabolism*
D002250:Carbon Radioisotopes; D004147:Dioxins; D000072317:Polychlorinated Dibenzodioxins; D014801:Vitamin A