Effects of dietary soy and estrous cycle on adrenal cytochrome p450 1B1 expression and DMBA metabolism in adrenal glands and livers in female Sprague-Dawley rats.
Cytochrome p450 1B1 (CYP1B1) has been shown to be important in the bioactivation of 7,12-dimethylbenz[a]anthracene (DMBA) to an adrenal toxin in rats. We investigated the effects of diet and stage of estrous cycle on CYP1B1 expression in rat adrenal glands and on DMBA metabolism by rat adrenal and hepatic microsomes. Female Sprague-Dawley (SD) rats were placed on either standard soy-containing NIH-31 rat chow or soy- and alfalfa-free 5K96 diet from postnatal day (PND) 21 until sacrifice at PND50+/-5. Stage of estrous at sacrifice was assessed by vaginal cytology and confirmed by histological examination of the vagina. Dietary soy at the level present in NIH-31 diet did not affect serum estrogen and progesterone levels. Immunohistochemical analysis confirmed that CYP1B1 was exclusively expressed in the zona fasciculata and zona reticularis in adrenal cortex, which are the regions vulnerable to DMBA-induced adrenal necrosis. Adrenal CYP1B1 protein expression, 3H-DMBA depletion, and formation of DMBA-3,4-, and -8,9-dihydrodiols by adrenal microsomes were greater in animals fed 5K96 diet, and the stage of the estrous cycle affected these parameters only in the soy-free 5K96 diet. In hepatic microsomes, the formation of DMBA-3,4-dihydrodiol, 7-hydroxy- and 12-hydroxy-DMBA were lower in animals fed NIH-31 diet than in those fed 5K96 diet. Thus, dietary soy and the estrous cycle appear to regulate adrenal CYP1B1 expression and DMBA metabolism by both adrenal and hepatic microsomes. The use of different basal diets containing variable levels of soy components may affect certain toxicity assessments.
Fu
Xin
X
Division of Biochemical Toxicology, National Center for Toxicological Research, Food and Drug Administration, 3900 NCTR Road, HFT-110, Jefferson, AR 72079, USA.
Blaydes
Betty S
BS
Weis
Constance C
CC
Latendresse
John R
JR
Muskhelishvili
Levan
L
Sutter
Thomas R
TR
Delclos
K Barry
KB
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000378:metabolism*; D000311:Adrenal Glands / Q000378:metabolism*; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism*; D015153:Blotting, Western; D002273:Carcinogens / Q000378:metabolism; D065633:Cytochrome P-450 CYP1B1; D004032:Diet; D004958:Estradiol / Q000097:blood; D004971:Estrus / Q000097:blood / Q000378:metabolism*; D005260:Female; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism*; D011374:Progesterone / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D045730:Soy Foods
D002273:Carcinogens; D011374:Progesterone; D004958:Estradiol; D015127:9,10-Dimethyl-1,2-benzanthracene; D001189:Aryl Hydrocarbon Hydroxylases; C585499:Cyp1b1 protein, rat; D065633:Cytochrome P-450 CYP1B1