Expression of 8-hydroxy-2'-deoxyguanosine in chronic liver disease and hepatocellular carcinoma.
Reactive oxygen species may be involved in the progression of chronic liver disease and the occurrence of hepatocellular carcinoma (HCC). To clarify whether clinicopathological findings in liver diseases are related to oxidative DNA damage, hepatic expression of the 8-hydroxy-2'-deoxyguanosine (8-OHdG) was examined in 75 liver disease patients, which included 32 chronic hepatitis (CH), 13 liver cirrhosis (LC) and 30 HCC patients. The CH patients had higher 8-OHdG-positive hepatocytes than LC (P < 0.05). In CH and LC, the number of 8-OHdG-positive hepatocytes was correlated with alanine aminotransferase and asparate aminotransferase (P < 0.01 and P < 0.05, respectively). Of 30 HCC cases, 25 cases (83%) showed stronger immunoreactivity than non-cancerous counterparts. The patients with poorly differentiated HCC had a larger tumor size and higher levels of AFP, and exhibited higher labeling indices of PCNA-, TUNEL- and 8-OHdG-positive cells than those with well and moderately differentiated HCC. Our findings suggest that oxidative DNA damage is increased in association with necroinflammation in chronic liver disease and determination of 8-OHdG is useful in assessing high-grade malignancy in HCC.
Ichiba
Miho
M
Division of Molecular and Genetic Medicine, Department of Genetic Medicine and Regenerative Therapeutics, Graduate School of Medicine, Faculty of Medicine, Tottori University, Yonago, Japan.
Maeta
Yoshiko
Y
Mukoyama
Tomoyuki
T
Saeki
Toshiya
T
Yasui
Sakiko
S
Kanbe
Takamasa
T
Okano
Jun-Ichi
J
Tanabe
Yoshinao
Y
Hirooka
Yasuaki
Y
Yamada
Sadako
S
Kurimasa
Akihiro
A
Murawaki
Yoshikazu
Y
Shiota
Goshi
G
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000328:Adult; D014408:Biomarkers, Tumor; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D002908:Chronic Disease; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008103:Liver Cirrhosis / Q000378:metabolism* / Q000473:pathology; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D017382:Reactive Oxygen Species / Q000378:metabolism
D014408:Biomarkers, Tumor; D017382:Reactive Oxygen Species; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine