2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN INDUCES DIVERSE RETINOIC ACID METABOLITES IN MULTIPLE TISSUES OF THE SPRAGUE-DAWLEY RAT

被引:23
作者
FIORELLA, PD
OLSON, JR
NAPOLI, JL
机构
[1] SUNY BUFFALO,SCH MED & BIOMED SCI,DEPT BIOCHEM,BUFFALO,NY 14214
[2] SUNY BUFFALO,SCH MED & BIOMED SCI,DEPT PHARMACOL & TOXICOL,BUFFALO,NY 14214
关键词
D O I
10.1006/taap.1995.1187
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
dRetinoic 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 mu g/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, [H-3]retinoic acid or [H-3]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. (C) 1995 Academic Press, Inc.
引用
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页码:222 / 228
页数:7
相关论文
共 44 条
[1]  
BLUMHOFF R, 1991, PHYSIOL REV, V71, P951
[2]   OVEREXPRESSION OF THE CELLULAR RETINOIC ACID BINDING PROTEIN-I (CRABP-I) RESULTS IN A REDUCTION IN DIFFERENTIATION-SPECIFIC GENE-EXPRESSION IN F9 TERATOCARCINOMA CELLS [J].
BOYLAN, JF ;
GUDAS, LJ .
JOURNAL OF CELL BIOLOGY, 1991, 112 (05) :965-979
[3]  
BOYLAN JF, 1992, J BIOL CHEM, V267, P21486
[4]  
BRADFORD MM, 1976, ANAL BIOCHEM, V72, P248, DOI 10.1016/0003-2697(76)90527-3
[5]   MARKED ALTERATIONS IN RETINOID HOMEOSTASIS OF SPRAGUE-DAWLEY RATS INDUCED BY A SINGLE IP DOSE OF 10-MU-G/KG OF 2,3,7,8-TETRACHLORODIBENZO-PARA-DIOXIN [J].
BROUWER, A ;
HAKANSSON, H ;
KUKLER, A ;
VANDENBERG, KJ ;
AHLBORG, UG .
TOXICOLOGY, 1989, 58 (03) :267-283
[6]   ALTERATIONS IN RETINOID CONCENTRATIONS IN SEVERAL EXTRAHEPATIC ORGANS OF RATS BY 3,4,3',4'-TETRACHLOROBIPHENYL [J].
BROUWER, A ;
KUKLER, A ;
VANDENBERG, KJ .
TOXICOLOGY, 1988, 50 (03) :317-330
[7]   CLONING OF A CDNA FOR LIVER MICROSOMAL RETINOL DEHYDROGENASE - A TISSUE-SPECIFIC, SHORT-CHAIN ALCOHOL-DEHYDROGENASE [J].
CHAI, XY ;
BOERMAN, MHEM ;
ZHAI, Y ;
NAPOLI, JL .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (08) :3900-3904
[8]   POLYCHLORINATED AND POLYBROMINATED BIPHENYL CONGENERS AND RETINOID LEVELS IN RAT-TISSUES - STRUCTURE-ACTIVITY-RELATIONSHIPS [J].
CHEN, LC ;
BERBERIAN, I ;
KOCH, B ;
MERCIER, M ;
AZAISBRAESCO, V ;
GLAUERT, HP ;
CHOW, CK ;
ROBERTSON, LW .
TOXICOLOGY AND APPLIED PHARMACOLOGY, 1992, 114 (01) :47-55
[9]  
DARJONO SSD, 1983, TOXICOL APPL PHARM, V71, P184
[10]  
DE LUCA LM, 1991, FASEB J, V5, P2924