@article{HBSN16119,
author = {Heidi Coia and Ning Ma and Aiwu Ruth He and Bhaskar Kallakury and Deborah L. Berry and Eva Permaul and Kepher H. Makambi and Ying Fu and Fung-Lung Chung},
title = {Detection of a lipid peroxidation-induced DNA adduct across liver disease stages},
journal = {Hepatobiliary Surgery and Nutrition},
volume = {7},
number = {2},
year = {2017},
keywords = {},
abstract = {Background: Oxidative stress and chronic inflammation can increase cellular levels of reactive oxygen species and lipid peroxidation (LPO) when associated with the pathogenesis of hepatocellular carcinoma (HCC), which can develop following the progression of steatosis, brosis and cirrhosis. Using a monoclonal antibody for cyclic γ-hydroxy-1, N2-propanodeoxyguanosine (γ-OHPdG), a promutagenic DNA adduct formed endogenously by LPO, we examined its formation across liver disease stages to understand it’s potential role in HCC development.
Methods: Formalin-fixed paraffin embedded (FFPE) liver tissue samples from 49 patients representing normal, steatosis, fibrosis, cirrhosis and HCC were stained for γ-OHPdG and 8-hydroxydeoxyguanosine (8-oxo-dG), an oxidative damage biomarker. Quantification of immunohistochemical (IHC) staining was performed using histological scoring of intensity and distribution. Using primary human hepatocytes (HH) and a stellate cell (SC) co-culture, immunocytochemical staining of γ-OHPdG and Nile Red was performed to determine if the formation of γ-OHPdG was consistent between the clinical sample disease stages and the in vitro steatotic and brotic conditions.
Results: γ-OHPdG levels varied significantly between the stages of normal and steatosis, steatosis and fibrosis, and steatosis and cirrhosis (P≤0.005). There was a trend, although not significant, of increased levels of γ-OHPdG in HCC compared to the other groups. A strong correlation was observed (Pearson’s, R2 =0.85) between levels of γ-OHPdG and 8-oxo-dG across the disease spectrum. The increase of γ-OHPdG in steatosis and decrease in brosis was a pattern con rmed in an in vitro model using primary HH co-cultured with human SCs.
Conclusions: γ-OHPdG was detected in FFPE liver tissues of patients with different stages of liver disease and in vitro studies, demonstrating that its formation is consistent with LPO in early stages of liver disease and suggesting that it may be a source of mutagenic DNA damage in liver disease progression.},
issn = {2304-389X}, url = {https://hbsn.amegroups.org/article/view/16119}
}