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Full-Text Articles in Medical Toxicology
Nucleotide Excision Repair: Impacts Of Environmental Carcinogens And Its Role In Cancer Susceptibility In Appalachian Kentucky, Nathaniel C. Holcomb
Nucleotide Excision Repair: Impacts Of Environmental Carcinogens And Its Role In Cancer Susceptibility In Appalachian Kentucky, Nathaniel C. Holcomb
Theses and Dissertations--Toxicology and Cancer Biology
Lung cancer is a particularly devastating disease, accounting for the most deaths among all cancer types in the United States. Despite a reduction in the country’s smoking rates, cigarette smoking remains the number one risk factor for lung cancer. Additionally arsenic exposure, which occurs primarily through contaminated drinking water in the U.S., is associated with increased lung cancer incidence. The nucleotide excision repair (NER) pathway is critical for maintenance of genomic fidelity, removing DNA lesions that could otherwise promote DNA mutations and drive carcinogenesis. Tobacco smoking introduces significant amounts of DNA damage and produces characteristic DNA mutations found in lung …
Arsenic Inhibits Dna Mismatch Repair By Promoting Egfr Expression And Pcna Phosphorylation, Dan Tong, Janice Ortega, Christine Kim, Jian Huang, Liya Gu, Guo-Min Li
Arsenic Inhibits Dna Mismatch Repair By Promoting Egfr Expression And Pcna Phosphorylation, Dan Tong, Janice Ortega, Christine Kim, Jian Huang, Liya Gu, Guo-Min Li
Toxicology and Cancer Biology Faculty Publications
Both genotoxic and non-genotoxic chemicals can act as carcinogens. However, while genotoxic compounds lead directly to mutations that promote unregulated cell growth, the mechanism by which non-genotoxic carcinogens lead to cellular transformation is poorly understood. Using a model non-genotoxic carcinogen, arsenic, we show here that exposure to arsenic inhibits mismatch repair (MMR) in human cells, possibly through its ability to stimulate epidermal growth factor receptor (EGFR)-dependent tyrosine phosphorylation of proliferating cellular nuclear antigen (PCNA). HeLa cells exposed to exogenous arsenic demonstrate a dose- and time-dependent increase in the levels of EGFR and tyrosine 211-phosphorylated PCNA. Cell extracts derived from arsenic-treated …