title: 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: Department of Anatomy, Faculty of Medicine, Kuwait University, Kuwait. Knarayana@hsc.edu.kw
authors: Kilarkaje
authors: K
authors: Narayana
authors: Raj
authors: R
authors: Raghupathy
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D004249:DNA Damage; D006151:Guanosine / Q000031:analogs & derivatives / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects* / Q000473:pathology; D020287:In Situ Nick-End Labeling; D007854:Lead / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D046529:Microscopy, Electron, Transmission; D009336:Necrosis; D009566:Nitrates / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar
chemical_list: D009566:Nitrates; D006151:Guanosine; D007854:Lead; C046215:8-hydroxyguanosine; C017461:lead nitrate