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

Drug and chemical toxicology (2011-10-13)
Kilarkaje Narayana, Raj Raghupathy
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Lead(II) nitrate, ACS reagent, ≥99.0%
Sigma-Aldrich
Lead(II) nitrate, 99.999% trace metals basis
Sigma-Aldrich
Lead(II) nitrate, ≥99.95% trace metals basis