Abstract
Human cytomegalovirus (HCMV) infection occurs early in life and viral persistence remains through life. An association between HCMV infection and malignant gliomas has been reported, suggesting that HCMV may play a role in glioma pathogenesis and could facilitate an accrual of genotoxic damage in the presence of γ-radiation; an established risk factor for gliomas. We tested the hypothesis that HCMV infection modifies the sensitivity of cells to γ-radiation-induced genetic damage. We used peripheral blood lymphocytes (PBLs) from 110 glioma patients and 100 controls to measure the level of chromosome damage and cell death. We evaluated baseline, HCMV-, γ-radiation and HCMV + γ-radiation induced genetic instability with the comprehensive Cytokinesis-Blocked Micronucleus Cytome (CBMN-CYT). HCMV, similar to radiation, induced a significant increase in aberration frequency among cases and controls. PBLs infected with HCMV prior to challenge with γ-radiation led to a significant increase in aberrations as compared to baseline, γ-radiation and HCMV alone. With regards to apoptosis, glioma cases showed a lower percentage of induction following in vitro exposure to γ-radiation and HCMV infection as compared to controls. This strongly suggests that, HCMV infection enhances the sensitivity of PBLs to γ-radiation-induced genetic damage possibly through an increase in chromosome damage and decrease in apoptosis.
Highlights
Malignant gliomas are the most common brain tumors in adults and are rapidly fatal [1,2]
The data presented in the current study suggest that Human cytomegalovirus (HCMV) infection induces genomic instabilities comparable to ionizing radiation; a known risk factor for glioma development
Our results indicate a significant increased sensitivity of peripheral blood lymphocytes (PBLs) to chromosomal aberrations in the presence of radiated HCMV cells
Summary
Malignant gliomas are the most common brain tumors in adults and are rapidly fatal [1,2]. Several studies have reported the effects of dysregulated cellular pathways in GBM development; in particular, alterations in cell proliferation and cell-cycle control resulting in apoptosis seem to be important pathways [4,5]. Bondy et al [11,12,13] and Lui et al [14], reported that exposure to ionizing radiation was consistently observed as an independent risk factor for brain tumors with higher levels of chromosome damage, with an increased sensitivity to radiation in glioma patients compared to controls. Studies by Edick et al [16] and Relling et al [17], have concluded that exposure to therapeutic cranial radiation is a likely risk factor for the development of secondary brain tumors of glial origin in cancer survivors
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