Fiorella P D, Olson J R, Napoli J L
Department of Biochemistry, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, New York 14214, USA.
Toxicol Appl Pharmacol. 1995 Oct;134(2):222-8. doi: 10.1006/taap.1995.1187.
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.
在单次腹腔注射2,3,7,8-四氯二苯并对二恶英（TCDD，5或80微克/千克）3天后，从雄性Sprague-Dawley大鼠的四种视黄酸靶组织制备微粒体，检测视黄酸代谢情况。来自所有四种组织的微粒体均催化视黄酸代谢速率增加，诱导程度顺序为：肝脏＞肺 = 肾脏 = 睾丸。这些反应在受影响的代谢产物、剂量效应以及所用底物（[3H]视黄酸或与细胞视黄酸结合蛋白结合的[3H]视黄酸）方面具有组织特异性。例如，睾丸中4-羟基视黄酸和18-羟基视黄酸均未增加；肝脏中4-羟基视黄酸增加而18-羟基视黄酸未增加；肾脏和肺中4-羟基视黄酸和18-羟基视黄酸均增加。TCDD能够影响多种组织中不同的视黄酸代谢产物，包括来自生理相关底物全细胞视黄酸结合蛋白的代谢产物，这增强了TCDD毒性的一个方面涉及改变视黄酸代谢的可能性。
