Mechanisms of adrenal damage induced by 7,12-dimethylbenz (alpha) anthrancene in female Sprague--Dawley rats.
The mechanisms of adrenal damage induced by 7,12-dimethylbenz (alpha) anthrancene (DMBA) in 50-day-old female Sprague--Dawley rats were investigated. A single dose of DMBA, either fed (30 mg) per os or injected (6 mg) in a caudal vein, caused inner cortical cell death (cells of the zonae fasciculata and reticularis) by an apoptotic mechanism. Apoptotic cells were identified by cell morphology, and terminal dUTP nick end labeling (TUNEL)-positive cells were seen at 12 hrs post-DMBA, reached a maximum at 36 h, and were accompanied by blood congestion followed by massive hemorrhage leading to post-apoptotic necrosis at 48 and 72 h. The apoptotic cascade involved the up-regulation of Bax, the down-regulation of Bcl-2, and the activation of caspase-3. At 72 h, regeneration as evidenced by the appearance of 5-bromo-2'-deoxyuridine-positive cells began to occur in the damaged inner cortical zones, with the cells proliferating toward the medulla thereafter. Regenerative cells expressed cytochrome P450 11 beta hydroxylase. The damage was repaired but calcification appeared at 2 weeks post-DMBA, leaving bow-shaped lesions in some adrenals.
Department of Pathology II, Kansai Medical University, Moriguchi, Osaka, 570-8506, Japan.
K
K
Tsuta
N
N
Shikata
S
S
Kominami
A
A
Tsubura
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity*; D000302:Adrenal Cortex / Q000187:drug effects*; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D002273:Carcinogens / Q000633:toxicity*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D015536:Down-Regulation; D005260:Female; D020287:In Situ Nick-End Labeling; D008854:Microscopy, Electron; D009929:Organ Size / Q000187:drug effects; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013252:Steroid 11-beta-Hydroxylase / Q000378:metabolism; D015854:Up-Regulation; D051028:bcl-2-Associated X Protein
C494828:Bax protein, rat; D002273:Carcinogens; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D015127:9,10-Dimethyl-1,2-benzanthracene; D013252:Steroid 11-beta-Hydroxylase; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases