title: Nuclear anomalies, chromosomal aberrations and proliferation rates in cultured lymphocytes of head and neck cancer patients.
abstract: Head and neck cancers (HNC) are extremely complex disease types and it is likely that chromosomal instability is involved in the genetic mechanisms of its genesis. However, there is little information regarding the background levels of chromosome instability in these patients. In this pilot study, we examined spontaneous chromosome instability in short-term lymphocyte cultures (72 hours) from 72 study subjects - 36 newly diagnosed HNC squamous cell carcinoma patients and 36 healthy ethnic controls. We estimated chromosome instability (CIN) using chromosomal aberration (CA) analysis and nuclear level anomalies using the Cytokinesis Block Micronucleus Cytome Assay (CBMN Cyt Assay). The proliferation rates in cultures of peripheral blood lymphocytes (PBL) were assessed by calculating the Cytokinesis Block Proliferation Index (CBPI). Our results showed a significantly higher mean level of spontaneous chromosome type aberrations (CSAs), chromatid type aberration (CTAs) dicentric chromosomes (DIC) and chromosome aneuploidy (CANEUP) in patients (CSAs, 0.0294±0.0038; CTAs, 0.0925±0.0060; DICs, 0.0213±0.0028; and CANEUPs, 0.0308±0.0035) compared to controls (CSAs, 0.0005±0.0003; CTAs, 0.0058±0.0015; DICs, 0.0005±0.0003; and CANEUPs, 0.0052±0.0013) where p<0.001. Similarly, spontaneous nuclear anomalies showed significantly higher mean level of micronuclei (MNi), nucleoplasmic bridges (NPBs) and nuclear buds (NBUDs) among cases (MNi, 0.01867±0.00108; NPBs, 0.01561±0.00234; NBUDs, 0.00658±0.00068) compared with controls (MNi, 0.00027±0.00009; NPBs, 0.00002±0.00002; NBUDs, 0.00011±0.00007).The evaluation of CBPI supported genomic instability in the peripheral blood lymphocytes showing a significantly lower proliferation rate in HNC patients (1.525±0.005552) compared to healthy subjects (1.686±0.009520 ) (p<0.0001). In conclusion, our preliminary results showed that visible spontaneous genomic instability and low rate proliferation in the cultured peripheral lymphocytes of solid tumors could be biomarkers to predict malignancy in early stages.
authors.affiliation: School of Bio Sciences and Technology, VIT University, Vellore, India E-mail : radhasaraswathy@vit.ac.in.
authors.forename: Alex
authors.initials: A
authors.lastname: George
authors.forename: Rupraj
authors.initials: R
authors.lastname: Dey
authors.forename: Vikas
authors.initials: V
authors.lastname: Bhuria
authors.forename: Shouvik
authors.initials: S
authors.lastname: Banerjee
authors.forename: Sivakumar
authors.initials: S
authors.lastname: Ethirajan
authors.forename: Ashok
authors.initials: A
authors.lastname: Siluvaimuthu
authors.forename: Radha
authors.initials: R
authors.lastname: Saraswathy
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology* / Q000235:genetics*; D002467:Cell Nucleus / Q000235:genetics; D049109:Cell Proliferation; D002478:Cells, Cultured; D002869:Chromosome Aberrations; D048749:Cytokinesis; D004249:DNA Damage; D005260:Female; D042822:Genomic Instability / Q000235:genetics*; D006258:Head and Neck Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D006801:Humans; D008214:Lymphocytes / Q000166:cytology* / Q000473:pathology; D008297:Male; D048629:Micronuclei, Chromosome-Defective; D015162:Micronucleus Tests; D008875:Middle Aged; D010865:Pilot Projects; D000077195:Squamous Cell Carcinoma of Head and Neck
chemical_list: D014408:Biomarkers, Tumor