Xeroderma pigmentosum, complementation group D expression in H1299 lung cancer cells following benzo[a]pyrene exposure as well as in head and neck cancer patients
| Autor: | Tzu-Fen Chen, Jau-Ling Huang, Wen-Yen Chiou, Yuan-Jen Lin, Ka-Wo Lee, Chang-Shen Lin |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
Adult
Male 0301 basic medicine Lung Neoplasms Xeroderma pigmentosum DNA Repair Ultraviolet Rays DNA repair DNA damage Health Toxicology and Mutagenesis Gene Expression Biology Toxicology Host-Cell Reactivation Histones 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Cell Line Tumor Benzo(a)pyrene polycyclic compounds medicine Humans RNA Neoplasm Carcinogen Aged Xeroderma Pigmentosum Group D Protein Aged 80 and over Xeroderma Pigmentosum Smoking Cancer Middle Aged medicine.disease Survival Analysis Molecular biology 030104 developmental biology chemistry Head and Neck Neoplasms 030220 oncology & carcinogenesis Carcinogens Environmental Pollutants Female Nucleotide excision repair |
| Zdroj: | Journal of Toxicology and Environmental Health, Part A. 79:39-47 |
| ISSN: | 1087-2620 1528-7394 |
| DOI: | 10.1080/15287394.2015.1104271 |
| Popis: | DNA repair genes play critical roles in response to carcinogen-induced and anticancer therapy-induced DNA damage. Benzo[a]pyrene (BaP), the most carcinogenic polycyclic aromatic hydrocarbon (PAH), is classified as a group 1 carcinogen by International Agency for Research on Cancer. The aims of this study were to (1) evaluate the effects of BaP on DNA repair activity and expression of DNA repair genes in vitro and (2) examine the role of xeroderma pigmentosum, complementation group D (XPD) mRNA expression in human head and neck cancers. Host cell reactivation assay showed that BaP inhibited nucleotide excision repair in H1299 lung cancer cells. DNA repair through the non-homologous end-joining pathway was not affected by BaP. Real-time quantitative reverse-transcription polymerase chain reaction (RT-PCR) and Western blot demonstrated that XPD was downregulated by BaP treatment. BaP exposure did not apparently affect expression of another 11 DNA repair genes. BaP treatment increased the DNA damage marker γ-H2AX and ultraviolet (UV) sensitivity, supporting an impairment of DNA repair in BaP-treated cells. XPD expression was also examined by quantitative RT-PCR in 68 head and neck cancers, and a lower XPD mRNA level was found in smokers’ cancer specimens. Importantly, reduced XPD expression was correlated with patient 5-year overall survival rate (35 vs. 56%) and was an independent prognostic factor (hazard ratio: 2.27). Data demonstrated that XPD downregulation was correlated with BaP exposure and human head and neck cancer survival. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|