DNA damage in peripheral blood lymphocytes of patients with cirrhosis related to alcohol abuse or to hepatitis B and C viruses.
BACKGROUND
Both alcohol abuse and hepatitis B or C virus infections are implicated in the development of hepatocellular carcinoma, but it is still controversial whether the pathogenetic mechanism is epigenetic or genotoxic.


OBJECTIVE
Considering that alcohol promotes the generation of reactive oxygen species and both viruses infect peripheral lymphocytes, in this study we investigated the occurrence of DNA fragmentation in peripheral blood lymphocytes from patients with alcoholic cirrhosis and from patients with cirrhosis related to B and C viruses, and analyzed the correlation between the degree of DNA fragmentation and the Child-Pugh score used to assess the degree of hepatic insufficiency.


METHODS
The study population consisted of two groups: group I involved 12 patients with alcoholic cirrhosis; group II involved 25 patients with hepatic B virus or hepatic C virus cirrhosis. The control group involved 20 healthy individuals. The degree of DNA fragmentation in peripheral blood lymphocytes was determined with the alkaline Comet assay that provides two indexes of the frequency of DNA single-strand breaks and alkali-labile sites, the tail length and the tail moment.


RESULTS
Mean values of both tail length and tail moment were significantly increased (P<0.001) in lymphocytes from 12 patients with alcoholic cirrhosis and in lymphocytes from 25 patients with HBV or HCV cirrhosis, as compared with average tail length and tail moment values of lymphocytes from 20 healthy individuals. A significant positive correlation was found to exist between the degree of DNA fragmentation present in lymphocytes of each of the 37 patients with alcoholic or viral cirrhosis and the corresponding value of the Child-Pugh score.


CONCLUSIONS
The occurrence of DNA fragmentation in peripheral blood lymphocytes reflects a direct genotoxic effect of either alcohol or HBV and HCV and suggests that the same genotoxic effect may operate in the liver and contribute to hepatocarcinogenesis.
Grossi
Sarah
S
Department of Internal Medicine, Clinical Pharmacology and Toxicology Unit, University of Genoa, Genoa, Italy.
Sumberaz
Alessandro
A
Gosmar
Marzia
M
Mattioli
Francesca
F
Testino
Gianni
G
Martelli
Antonietta
A
D006528:Carcinoma, Hepatocellular / Q000235:genetics; D020552:Comet Assay / Q000379:methods; D053938:DNA Fragmentation; D005260:Female; D006509:Hepatitis B / Q000150:complications*; D006526:Hepatitis C / Q000150:complications*; D006801:Humans; D008104:Liver Cirrhosis, Alcoholic / Q000235:genetics*; D008113:Liver Neoplasms / Q000235:genetics; D008214:Lymphocytes; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000276:immunology