Inhibition of apoptosis during 2,3,7,8-tetrachlorodibenzo-p-dioxin-mediated tumour promotion in rat liver.
The effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on cell division and cell death (apoptosis) in glutathione S-transferase (GST-P)-positive liver foci were analyzed in diethylnitrosamine-initiated female Wistar rats that were treated with TCDD, either acutely for 3 days or chronically for 115 days. Apoptotic bodies were quantitated in liver sections simultaneously stained for GST-P expression and H&E using a novel fluorescence microscopic detection method which greatly facilitates recognition of apoptotic bodies due to their high level of eosin fluorescence. While TCDD treatment only marginally affected cell division in GST-P-positive liver foci, as estimated by 5-bromo-2'-deoxyuridine-labelling, apoptotic indices were decreased to approximately 60% and approximately 10% of control values after acute and chronic TCDD treatment, respectively. In normal liver tissue, apoptotic indices were only slightly reduced by TCDD treatment, suggesting selective inhibition of apoptosis in the enzyme-altered cell population by the dioxin. Since inhibition of apoptosis in GST-P-positive liver foci was by far more pronounced than changes in cell division, our data suggest that the promoting activity of TCDD is preferentially mediated by a decrease of apoptosis in enzyme-altered liver foci.
Stinchcombe
S
S
Institute of Toxicology, University of Tübingen, Germany.
Buchmann
A
A
Bock
K W
KW
Schwarz
M
M
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D005260:Female; D005982:Glutathione Transferase / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000187:drug effects*; D008856:Microscopy, Fluorescence / Q000379:methods; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D011230:Precancerous Conditions / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar
D000072317:Polychlorinated Dibenzodioxins; D005982:Glutathione Transferase