Time and dose responses of the reduction in retinoid concentrations in C57BL/Rij and DBA/2 mice induced by 3,4,3',4'-tetrachlorobiphenyl.
A single ip dose of 15 mg 3,4,3',4'-tetrachlorobiphenyl (TCB)/kg induced a 30 to 40% reduction of retinol and retinyl palmitate concentrations in hepatic tissue of C57BL/Rij mice within 2 to 4 days. This level of reduction was maintained for about 14 days. The ED50 was 32 mg TCB/kg for hepatic retinol and 17 mg TCB/kg for hepatic retinyl palmitate. In DBA/2 mice, however, no reduction in hepatic retinoids was observed even at doses up to 729 mg TCB/kg. The duration of the reduction in hepatic retinoids did not correlate with the induced aryl hydrocarbon hydroxylase (AHH) activity in C57BL/Rij mice. These data suggest that AHH and related enzymes are not directly involved in the TCB-induced reduction in retinoids in these mouse strains. No significant differences in the accumulation of TCB in hepatic tissues of C57BL/Rij and DBA/2 mice were observed; however, the estimated elimination rate in C57BL/Rij was two times faster than that in DBA/2 mice. In serum of DBA/2 mice, a rapid 50% decline in the concentration of retinol was observed after only 2 to 6 hr, remaining at the reduced value for about 14 days. The ED50 for serum retinol was 1 to 2 mg TCB/kg. Only a transient reduction in serum retinol, disappearing within 48 hr, was observed in the C57BL/Rij mouse. TCB accumulated to an almost 15-fold higher extent in serum of DBA/2 mice as compared with C57BL/Rij mice. The effect of TCB on retinoids in a few other strains of mice and in the Sprague-Dawley rat showed a reduction in serum retinol rather than in hepatic retinoids.
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000096:biosynthesis; D004224:Diterpenes; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D011078:Polychlorinated Biphenyls / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012176:Retinoids / Q000378:metabolism*; D000084562:Retinyl Esters; D013045:Species Specificity; D013997:Time Factors; D014801:Vitamin A / Q000031:analogs & derivatives / Q000097:blood / Q000378:metabolism
D004224:Diterpenes; D012176:Retinoids; D000084562:Retinyl Esters; D014801:Vitamin A; C014794:retinol palmitate; D011078:Polychlorinated Biphenyls; D001189:Aryl Hydrocarbon Hydroxylases; C028451:3,4,3',4'-tetrachlorobiphenyl