DNA damage checkpoint response to aflatoxin B1
| Autor: | Atilla Engin, Ayse Basak Engin |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Genome instability
Aflatoxin B1 Carcinoma Hepatocellular Carcinogenesis Guanine Health Toxicology and Mutagenesis Mutant Ataxia Telangiectasia Mutated Proteins 010501 environmental sciences Toxicology medicine.disease_cause 01 natural sciences 03 medical and health sciences chemistry.chemical_compound medicine Animals Humans 030304 developmental biology 0105 earth and related environmental sciences Pharmacology 0303 health sciences Mutation Chemistry Point mutation Liver Neoplasms Receptors Death Domain General Medicine G2-M DNA damage checkpoint Cell cycle Molecular biology Oxidative Stress DNA DNA Damage |
| Zdroj: | Environmental Toxicology and Pharmacology. 65:90-96 |
| ISSN: | 1382-6689 |
| DOI: | 10.1016/j.etap.2018.12.006 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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