FEMALE SPRAGUE-DAWLEY RATS EXPOSED TO A SINGLE ORAL DOSE OF 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN EXHIBIT SUSTAINED DEPLETION OF ARYL-HYDROCARBON RECEPTOR PROTEIN IN LIVER, SPLEEN, THYMUS, AND LUNG
Rs. Pollenz et al., FEMALE SPRAGUE-DAWLEY RATS EXPOSED TO A SINGLE ORAL DOSE OF 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN EXHIBIT SUSTAINED DEPLETION OF ARYL-HYDROCARBON RECEPTOR PROTEIN IN LIVER, SPLEEN, THYMUS, AND LUNG, TOXICOLOGICAL SCIENCES, 42(2), 1998, pp. 117-128
There is currently little information concerning the time-dependent re
lationship between 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure
and aryl hydrocarbon receptor (AHR) and aryl hydrocarbon receptor nuc
lear translocator (ARNT) protein concentration in vivo. Therefore, fem
ale Sprague-Dawley rats were given a single oral dose of TCDD (10 mu g
/kg), and the AHR and ARNT protein concentrations in liver, spleen, th
ymus, and lung determined by Western blotting. In liver, the concentra
tion of AHR protein was significantly reduced 8 and 24 h postdosing as
compared to time-matched controls. In spleen and lung, the concentrat
ion of AHR protein was reduced 3, 8, 24, and 168 h posttreatment compa
red to time-matched controls but returned to control levels by 336 h.
In thymus, reductions in AHR protein concentration were observed 8, 24
, 168, and 336 h postdosing as compared to time-matched controls. Sign
ificant reductions in the concentration of ARNT protein were not obser
ved in any of the TCDD-exposed tissues. Functional studies in cell cul
ture showed that exposure of a mouse hepatoma cell line (Hepa-1c1c7) a
nd a rat smooth muscle cell line (A-7) to TCDD (1 nM) for 12 days resu
lted in a 50% reduction in TCDD-inducible reporter gene expression fol
lowing subsequent challenge by an additional dose of TCDD (1 nM). Coll
ectively, these results show that (i) TCDD-mediated depletion of AHR o
ccurs in vivo, (ii) AHR protein does not rapidly recover to pretreatme
nt levels even though the tissue concentration of TCDD has fallen, and
(iii) reduction in AHR protein concentration correlates with reductio
n in TCDD-mediated reporter gene expression in mammalian culture cells
. (C) 1998 Society of Toxicology.