The Role Of Genetic Polymorphism Of Alcohol Dehydrogenase 2 In Alcohol-related Oxidative Stress Of Peripheral Blood Lymphocytes From Primary Hepatocellular Carcinoma And The Response To Percutaneous Ethanol Injection In Guangxi, China

Objective: To study the effect of genetic polymorphism of alcohol dehydrogenase 2 on the alcohol-related oxidative stress,and further explore the role of genetic polymorphism of alcohol dehydrogenase 2 in modulating individual response to percutaneous ethanol injection (PEI).Methods:1.Peripheral blood lymphocytes were collected from 20 HCC patients and 10 healthy people. Intracellular superoxide dismutase (SOD),lipid peroxidation products-malondialdehyde (MDA),hydroxyl radicals (OH-) and reactive oxygen species (ROS) with regard to gradient doses of ethanol were determined to evaluate the antioxidant capacity of ethanol, the level of lipid peroxidation and the oxidative effects in cultured cells. In addition, the genotype of ethanol metabolism ADH2 were detected by PCR-RFLP assay.2.Twenty patients with focal hepatic lesions received PEI.Serum ALT,AST and GGT were monitored pre and post PEI, and the genotypes of ADH2 gene were detected using PCR-RFLP assay.Results:1. After ethanol incubation, OH-, MDA and ROS in the supernatant increased with ethanol concentration in a dose-dependent manner. OH- levels is significant higher than the blank control in all ethanol concentration group (P<0.01). MDA levels is significant higher than the blank control at 100mmol/L ethanol concentration (P<0.01). For ROS levels is significant higher than the blank control at 200mmol/L ethanol concentration (P<0.01). SOD in the supernatant decreased with ethanol concentration in a dose-dependent manner, its levels is significant lower than the blank control at 200mmol/L ethanol concentration (P<0.01). Oxidative damage levels in individuals carrying ADH2*1 genotypes were similar to those carrying ADH2*2 and ADH2*3 genotypes (P>0.05).2.Serum levels of ALT and AST in patients significantly increased after PEI intervention (P<0.01).But there was no statisticant significance with different genotype of ADH2 affect to hepatic function (P>0.05).Conclusion:1.Upon exposure to low-concentration ethanol, lymphocytes damage was induced mainly by excessive generation of OH-.2.There was no significant difference of oxidative damage and anti-oxidant capability in lymphocytes exposed to low-concentration ethanol among different ADH2 genotype carriers.3.Ethanol exposure leads to hepatic injury via the toxicity of its metabolites-acetaldehyde and free radicals. But in this study, the ADH2 genotype is not a significant contributor to liver function alteration in patients received PEI treatment.