Roles of alcohol and tobacco exposure in the development of hepatocellular carcinoma
| Autor: | Vishnudutt Purohit, Byoung Joon Song, Oh Sang Kwon, Rao S. Rapaka |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Carcinoma
Hepatocellular Alcohol Drinking medicine.disease_cause Antioxidants Article General Biochemistry Genetics and Molecular Biology Proinflammatory cytokine Lipid peroxidation chemistry.chemical_compound Risk Factors medicine Animals Humans General Pharmacology Toxicology and Pharmaceutics Carcinogen chemistry.chemical_classification Reactive oxygen species Ethanol Liver Neoplasms Smoking Kupffer cell General Medicine CYP2E1 medicine.disease Oxidative Stress medicine.anatomical_structure chemistry Biochemistry Cancer research Inflammation Mediators Reactive Oxygen Species Liver cancer Oxidative stress |
| Zdroj: | Life Sciences. 92:3-9 |
| ISSN: | 0024-3205 |
| DOI: | 10.1016/j.lfs.2012.10.009 |
| Popis: | The purpose of this report is to summarize the roles of alcohol and tobacco exposure in the development of hepatocellular carcinoma (HCC). Chronic heavy alcohol exposure is a major risk factor for HCC, which is the most frequent type of liver cancer. Alcohol ingestion may initiate and or promote the development of HCC by: 1) acetaldehyde-DNA adduct formation; 2) cytochrome P4502E1-associated reactive oxygen species (ROS) generation , lipid peroxidation, p53 mutation, and conversion of pro-carcinogens to carcinogens; 3) iron accumulation that leads to ROS generation, lipid peroxidation, p53 mutation, and initiation of inflammatory cascade via nuclear factor-KappaB (NF-kB) activation; 4) glutathione depletion leading to oxidative stress; 5) s-adenosylmethionine (SAM) depletion and associated DNA hypomethylation of oncogenes ; 6) retinoic acid depletion and resultant hepatocyte proliferation via up-regulation of activator protein-1 (AP-1); 7) initiating an inflammatory cascade through increased transfer of endotoxin from intestine to liver, Kupffer cell activation via CD14/toll-like receptor-4 (TLR-4), oxidative stress, NF-kB or early growth response-1(Egr-1) activation, and generation of inflammatory cytokines and chemokines; 8) induction of liver fibrosis; and 9) decreasing the number and/or function of natural killer cells. Tobacco exposure is also a risk factor for HCC. It may contribute to the initiation and promotion of HCC due the presence of mutagenic and carcinogenic compounds as well as by causing oxidative stress due to generation of ROS and depletion of endogenous antioxidants. Simultaneous exposure to alcohol and tobacco is expected to promote the development of HCC in an additive and/or synergistic manner. |
| Databáze: | OpenAIRE |
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