2,3,7,8-Tetrachlorodibenzo-p-dioxin induces diverse retinoic acid metabolites in multiple tissues of the Sprague-Dawley rat.
Retinoic acid metabolism was examined in microsomes prepared from four retinoid target tissues of male Sprague-Dawley rats removed 3 days after a single exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, 5 or 80 micrograms/kg, ip). Microsomes from all four tissues catalyzed increased rates of retinoic acid metabolism, with the degree of induction following the order: liver > lung = kidney = testis. The responses were tissue-specific with respect to the metabolites affected, the effects of dose, and the substrate used, [3H]retinoic acid or [3H]retinoic acid bound with cellular retinoic acid-binding protein. For example, neither 4-hydroxy- nor 18-hydroxy-retinoic acid increased in testis; 4-hydroxy- but not 18-hydroxy-retinoic acid increased in liver; and both 4-hydroxy- and 18-hydroxy-retinoic acid increased in kidney and lung. This ability of TCDD to affect diverse retinoic acid metabolites in multiple tissues, including those from a physiologically relevant substrate, holocellular retinoic-acid binding protein, strengthens the possibility that one aspect of TCDD toxicity involves altering the metabolism of retinoic acid.
Fiorella
P D
PD
Department of Biochemistry, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, New York 14214, USA.
Olson
J R
JR
Napoli
J L
JL
D000818:Animals; D008297:Male; D008861:Microsomes / Q000378:metabolism; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D014212:Tretinoin / Q000378:metabolism*
D000072317:Polychlorinated Dibenzodioxins; D018168:Receptors, Retinoic Acid; D014212:Tretinoin