Accelerated Repair and Reduced Mutagenicity of DNA Damage Induced by Cigarette Smoke in Human Bronchial Cells Transfected with E.coli Formamidopyrimidine DNA Glycosylase

Abstract

Cigarette smoke (CS) is associated to a number of pathologies including lung cancer. Its mutagenic and carcinogenic effects are partially linked to the presence of reactive oxygen species and polycyclic aromatic hydrocarbons (PAH) inducing DNA damage. The bacterial DNA repair enzyme formamidopyrimidine DNA glycosylase (FPG) repairs both oxidized bases and different types of bulky DNA adducts. We investigated in vitro whether FPG expression may enhance DNA repair of CS-damaged DNA and counteract the mutagenic effects of CS in human lung cells. NCI-H727 non small cell lung carcinoma cells were transfected with a plasmid vector expressing FPG fused to the Enhanced Green Fluorescent Protein (EGFP). Cells expressing the fusion protein EGFP-FPG displayed accelerated repair of adducts and DNA breaks induced by CS condensate. The mutant frequencies induced by low concentrations of CS condensate to the Na+K+-ATPase locus (ouar) were significantly reduced in cells expressing EGFP-FPG. Hence, expression of the bacterial DNA repair protein FPG stably protects human lung cells from the mutagenic effects of CS by improving cells’ capacity to repair damaged DNA.

Monocyte-derived exosomes upon exposure to cigarette smoke condensate alter their characteristics and show protective effect against cytotoxicity and HIV-1 replication

“…Although U937 and U1 are authentic cell lines for uninfected and HIV-1 infected cell lines, respectively 31 , 48 , we further investigated the effects of CSC/CSC-exosomes on viral replication and cytotoxicity in HIV-1 infected primary human macrophages (PHM) obtained from a healthy donor. Based on the previously described protocol for exosomal entry into macrophages 49 and our uptake study on U937-macrophages (Fig.…”

“…We performed an initial screening of whether U937 monocytic cell-derived exosomes carry CYPs or AOEs (mRNA and/or protein). The role of cellular CYPs and AOEs in tobacco-mediated oxidative stress, cytotoxicity, and carcinogenesis is well-established 48 . Our previous study has also suggested a potential role of CYP and oxidative stress pathways in smoking-mediated HIV-1 replication 24 .…”

Genetic Instability among Hitnü People Living in Colombian Crude-Oil Exploitation Areas

“…However, in concordance with the results obtained for NPB, NBUDS, APOP, and NECRO, other studies have suggested a protective effect of tobacco exposure via an individual adaptative response in exposed individuals. In vivo evidence has shown that glutathione is elevated in the lung epithelium of mice as a response to inhaled tobacco smoke [ 36 ]. In addition, DNA base excision capacity seems to increase this adaptative response from a mechanical point of view.…”

Attenuation of Polycyclic Aromatic Hydrocarbon (PAH)-Mediated Pulmonary DNA Adducts and Cytochrome P450 (CYP)1B1 by Dietary Antioxidants, Omega-3 Fatty Acids, in Mice

“…The formation of PAH-DNA adducts can be attenuated by detoxification of parent PAHs. PAH-DNA-bound adducts can also be removed by DNA repair processes [ 17 , 18 , 19 , 20 ], and injured cells can be eliminated by cell death including necrosis and apoptosis [ 21 , 22 , 23 ]. During chronic exposures, DNA damage can readily reach steady-state levels in target tissues.…”