Exposure to Environmental Mutagens: APC and Colorectal Carcinogenesis

摘要: Environmental mutagens are global health hazards and a major risk factor for colon cancer development. include variety of genotoxic carcinogenic compounds including polycyclic aromatic hydrocarbons, heterocyclic amines, nitrosamines, amines. Their sources pollution, diet, alcohol cigarette smoke. These come in contact with large bowel through blood circulation or direct ingestion. Once these DNA the gut epithelial cells, they form DNA-adducts. If damage exceeds repair capacity then persistence mutations can lead to transformation cells. Mutations adenomatous polyposis coli (APC) gene is considered be one earliest events genesis colorectal cancer, its role has been well documented broad spectrum functions ranging from cell adhesion migration, regulation Wnt/β-catenin-signaling pathway, cycle control, apoptosis, chromosomal segregation at mitosis. The contribution environmental on APC very scanty literature. In past several years, we have initiated studies examine interaction pathways induced by mutagens. We showed that transcriptionally upregulated after subsequent exposure smoking. addition, recently discovered novel base excision (BER) pathway. interacts polymerase β Fen-1 blocks Pol-β-directed BER. Thus, APC-mediated block BER response mutagens, especially DNA-alkylating agents, detrimental cell.