Gazi University, Faculty of Pharmacy, Department of Toxicology, Ankara, Turkey.
Gazi University, Faculty of Medicine, Department of General Surgery, Ankara, Turkey.
Environ Toxicol Pharmacol. 2019 Jan;65:90-96. doi: 10.1016/j.etap.2018.12.006. Epub 2018 Dec 7.
Although most countries regulate the aflatoxin levels in food by legislations, high amounts of aflatoxin B1 (AFB1)-DNA adducts can still be detected in normal and tumorous tissue obtained from cancer patients. AFB1 cannot directly interact with DNA unless it is biotransformed to AFB1-8, 9-epoxide via cytochrome p450 enzymes. This metabolite spontaneously and irreversibly attaches to guanine residues to generate highly mutagenic DNA adducts. AFB1-induced mutation of ATM kinase results in the deterioration of the cell cycle checkpoint activation at the G2/M checkpoint site. Genomic instability and increased cancer risk due to A-T mutation is the result of diminished repair of DNA double strand breaks. The major point mutation caused by AFB1 is G-to-T transversion that is related with the high frequency of p53 mutation. Majority of AFB1 associated hepatocellular cancer cases carry TP53 mutant DNA, which is an indicator of AFB1 exposure, as well as hepatocellular cancer risk.
尽管大多数国家通过立法来规范食品中的黄曲霉毒素水平，但仍能在癌症患者的正常和肿瘤组织中检测到大量的黄曲霉毒素 B1（AFB1）-DNA 加合物。AFB1 不能直接与 DNA 相互作用，除非它通过细胞色素 p450 酶生物转化为 AFB1-8,9-环氧化物。这种代谢物会自发且不可逆地与鸟嘌呤残基结合，生成具有高度致突变性的 DNA 加合物。AFB1 诱导 ATM 激酶突变会导致 G2/M 检验点处细胞周期检验点激活的恶化。由于 A-T 突变，基因组不稳定性和癌症风险增加是由于 DNA 双链断裂修复减少所致。AFB1 引起的主要点突变是 G 到 T 的颠换，与 p53 突变的高频相关。大多数与 AFB1 相关的肝细胞癌病例携带 TP53 突变型 DNA，这是 AFB1 暴露以及肝细胞癌风险的一个指标。
