DNA damage and cellular abnormalities in tuberculosis, lung cancer and chronic obstructive pulmonary disease

Abstract

BackgroundTuberculosis (TB), Lung Cancer (LC) and Chronic Obstructive Pulmonary Diseases (COPD) affect millions of individuals worldwide. Monitoring of DNA damage in pathological situations has been investigated because it can add a new dimension to clinical expression and may represent a potential target for therapeutic intervention. The aim of this study was to evaluate DNA damage and the frequency of cellular abnormalities in TB, LC and COPD patients by comparing them to healthy subjects.MethodsThe detection of DNA damage by a buccal micronucleus cytome assay was investigated in patients with COPD (n = 28), LC (n = 18) and TB (n = 22) and compared to control individuals (n = 17).ResultsThe COPD group had a higher frequency of apoptotic cells compared to TB and LC group. The TB group showed a higher frequency of DNA damage, defect in cytokinesis, apoptotic and necrotic cells. Patients with LC had low frequency of chromosomal aberrations than TB and COPD patients.ConclusionCOPD patients showed cellular abnormalities that corresponded to cell death by apoptosis and necrosis, while patients with TB presented defects in cytokinesis and dysfunctions in DNA repair that resulted in the formation of micronucleus (MN) besides apoptotic and necrotic cells. Patients with COPD, TB and LC had a low frequency of permanent DNA damage.

Chronic obstructive pulmonary disease among lung cancer-free smokers: The importance of healthy controls

“…These reported findings, unlike ours, were highly significant for the COPD patients, since their study was designed specifically to recruit COPD patients with different stages of the disease (moderate to very severe COPD), who were diagnosed via clinical history, physical examination, and spirometry. In a recent study on buccal cells, da Silva et al [26] reported the presence of apoptosis and necrosis among clinically diagnosed COPD patients. In our study, we used a convenience sample of self-reported COPD participants, recruited through an on-going lung cancer study, as part of the smoker control group.…”

Mycobacterium tuberculosis promotes genomic instability in macrophages

“…We observed nuclear abnormalities associated with MN formation (nucleoplasmic bridge, nuclear buds, and blebbing) in M. tuberculosis -infected macrophages ( da Silva et al 2015 , Mohanty et al 2016 ). These abnormalities are indicative of the genome damage events and considered as biomarkers of genotoxic events and chromosomal instability ( Fenech et al 2011 ).…”

“…Previous studies have demonstrated DNA damage in untreated TB patients using chromosomal abnormalities, MN techniques ( Rao et al 1990 , Masjedi et al 2000 , da Silva et al 2015 ), and comet assay ( Selek et al 2012 ).…”

Whole-Exome Sequencing Identifies the 6q12-q16 Linkage Region and a Candidate Gene, TTK, for Pulmonary Nontuberculous Mycobacterial Disease

“…Depletion of hMps1 causes a defect in G 2 /M arrest, compromising DNA repair and cell survival (40)(41)(42). Dysfunction in DNA repair is a common finding in patients with COPD and tuberculosis (43). As studies on TTK/hMps1 have been exclusively focused on its tumorigenesis, its contribution to bronchiectasis; to bacterial, mycobacterial, or fungal infections; or overall progression to pulmonary disease is currently unknown.…”