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

作者：Lin, Chang Shen^*; Chiou, Wen Yen; Lee, Ka Wo; Chen, Tzu Fen; Lin, Yuan Jen; Huang, Jau Ling^*

来源：Journal of Toxicology and Environmental Health Part A: Current Issues , 2016, 79(1): 39-47.

DOI：10.1080/15287394.2015.1104271

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 (FIT-PCII) and Western blot demontrated that XPD was doxivnregulated by BaP treatment. BaP exposure did not apparently affect expression of another 11 DNA repair, genes. BaP treatment increased the DNA damage marker gamma-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 xpression was correlated with patient S-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.

• 出版日期2016
• 单位河北医科大学; 中山大学