DNA damage in lead-exposed hepatocytes: coexistence of apoptosis and necrosis?

Abstract

The aim of the present study was to investigate the coexistence of oxidative DNA damage and apoptosis- and necrosis-related DNA damage, and to correlate with ultrastructural changes in hepatocyte nuclei in the lead-nitrate-exposed liver. Adult male Wistar rats were exposed to 0, 0.5, and 1% lead nitrate for 60 days, and the livers were sampled the next day. Ultrastructurally, hepatocyte nuclei showed no apoptosis-related morphological changes, but showed necrotic changes. Competitive enzyme-linked immunosorbent assay showed no change in 8-oxo-dG activity (P > 0.05), but immunohistochemistry showed its localization in hepatocytes, Kupffer cells, endothelium, and bile ductule epithelium. TUNEL-labeled DNA breaks presenting 3'-OH ends increased in hepatocytes in all functional zones of the portal acini and bile ductule epithelium (zones I>III>II). In situ oligo ligation revealed the existence of DNA breaks bearing duplex 3' overhangs and 5' P-blunt ends in hepatocytes of all functional zones and bile ductule epithelium. In conclusion, both apoptosis- and necrosis-related DNA damage coexist without significant oxidative DNA damage. Hepatocytes display changes related to necrosis, but not those related to apoptosis.

• Authors: Kilarkaje Narayana, Raj Raghupathy
• Journal: Drug and chemical toxicology (Drug Chem Toxicol) Vol. 35 Issue 2 Pg. 208-17 (Apr 2012) ISSN: 1525-6014 [Electronic] United States
• PMID: 21988076 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Nitrates
• Guanosine
• Lead
• 8-hydroxyguanosine
• lead nitrate

Topics

• Animals
• Apoptosis (drug effects, genetics)
• DNA Damage
• Guanosine (analogs & derivatives, metabolism)
• Hepatocytes (drug effects, pathology)
• In Situ Nick-End Labeling
• Lead (pharmacology)
• Liver (drug effects, pathology)
• Male
• Microscopy, Electron, Transmission
• Necrosis
• Nitrates (pharmacology)
• Random Allocation
• Rats
• Rats, Wistar