Dietary modulation of 7,12-dimethylbenz[a]anthracene (DMBA)-induced adrenal toxicity in female Sprague-Dawley rats.
In this study, dietary modulation of 7,12-dimethylbenz[a]anthracene (DMBA)-induced adrenal toxicity in rats was investigated. Beginning at postnatal day (PND) 21, female Sprague-Dawley rats were fed either soy-containing NIH-31 diet or soy- and alfalfa-free 5K96 diet. On the first day of diestrus when the animals were PND 50 +/- 5, rats received either an oral dose of 80 mg/kg DMBA or sesame oil, the vehicle, and were sacrificed at 24, 36, or 48 h after treatment. Apoptosis was manifested at 24 and 36 h after DMBA treatment in the zona reticularis (ZR) and the zona fasciculata (ZF) of the adrenal cortex; this was followed by severe hemorrhagic necrosis at 48 h. DMBA-induced apoptosis, evaluated by the TUNEL assay, immunohistochemical analysis of activated caspase 3, and the ratio of expression of pro-apoptotic Bax to anti-apoptotic Bcl2, was greater in rats fed NIH-31 diet relative to rats fed 5K96 diet at 24 h after treatment. Four of six DMBA-treated rats fed 5K96 diet had severe adrenal necrosis by 48 h, whereas this lesion was present in only two of six DMBA-treated rats fed NIH-31 diet. DMBA also caused a significant decrease of serum corticosterone relative to controls at 48 h in rats fed 5K96 diet. The present study indicated that diet modulates DMBA-induced adrenal toxicity in female rats, with increased apoptosis early and reduced necrosis later in rats fed a soy-containing diet.
Fu
Xin
X
Division of Biochemical Toxicology, National Center for Toxicological Research, Food and Drug Administration, 3900 NCTR Road, Jefferson, AR 72079, USA.
Latendresse
John R
JR
Muskhelishvili
Levan
L
Blaydes
Betty S
BS
Delclos
K Barry
KB
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity*; D000284:Administration, Oral; D000302:Adrenal Cortex / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002273:Carcinogens / Q000633:toxicity*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D003345:Corticosterone / Q000097:blood; D004032:Diet; D005260:Female; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D009336:Necrosis / Q000139:chemically induced; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D045730:Soy Foods; D013997:Time Factors; D051028:bcl-2-Associated X Protein
C494828:Bax protein, rat; D002273:Carcinogens; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D015127:9,10-Dimethyl-1,2-benzanthracene; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; D003345:Corticosterone