在 hepatocellular 癌的化学致癌物和基因变化的相互作用

• 作者: Yu-Jing Zhang
• 来源期刊: 世界肝病学杂志：英文版（电子版）
• 学科: 医学
• 关键词: HEPATOCELLULAR carcinoma Chemical CARCINOGENS Aflatoxin B 1 POLYCYCLIC aromatic hydrocarbons 4-aminobiphenyl HEPATITIS B VIRUS HEPATITIS C VIRUS Glutathione S -transferase Cytochrome p450 enzymes Genetic variation
• 年，卷（期）: 2010,（3）
• 页码范围: 94-102
• 页数: 9页
• 分类号: R735.7

摘要

In the etiology of hepatocellular carcinoma (HCC), in addition to hepatitis B virus and hepatitis C virus infections, chemical carcinogens also play important roles. For example, aflatoxin B 1 (AFB 1 ) epoxide reacts with guanine in DNA and can lead to genetic changes. In HCC, the tumor suppressor gene p53 codon 249 mutation is associated with AFB 1 exposure and mutations in the K -ras oncogene are related to vinyl chloride exposure. Numerous genetic alterations accumulate during the process of hepatocarcinogenesis. Chemical carcinogen DNA-adduct formation is the basis for these genetic changes and also a molecular marker which reflects exposure level and biological effects. Metabolism of chemical carcinogens, including their activation and detoxification, also plays a key role in chemical hepatocarcinogenesis. Cytochrome p450 enzymes, N -acetyltransferases and glutathione S -transferases are involved in activating and detoxifying chemical carcinogens. These enzymes are polymorphic and genetic variation influences biological response to chemical carcinogens. This genetic variation has been postulated to influence the variability in risk for HCC observed both within and across populations. Ongoing studies seek to fully understand the mechanisms by which genetic variation in response to chemical carcinogens impacts on HCC risk.