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 g-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.
Keywords: HCMV; brain tumors; CBMN-CYT assay; chromosome aberrations
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Rourke, E.A.; Lopez, M.S.; Monroy, C.M.; Scheurer, M.E.; Etzel, C.J.; Albrecht, T.; Bondy, M.L.; El-Zein, R.A. Modulation of Radiation-Induced Genetic Damage by HCMV in Peripheral Blood Lymphocytes from a Brain Tumor Case-Control Study. Cancers 2010, 2, 420-435.
Rourke EA, Lopez MS, Monroy CM, Scheurer ME, Etzel CJ, Albrecht T, Bondy ML, El-Zein RA. Modulation of Radiation-Induced Genetic Damage by HCMV in Peripheral Blood Lymphocytes from a Brain Tumor Case-Control Study. Cancers. 2010; 2(2):420-435.
Rourke, Elizabeth A.; Lopez, Mirtha S.; Monroy, Claudia M.; Scheurer, Michael E.; Etzel, Carol J.; Albrecht, Thomas; Bondy, Melissa L.; El-Zein, Randa A. 2010. "Modulation of Radiation-Induced Genetic Damage by HCMV in Peripheral Blood Lymphocytes from a Brain Tumor Case-Control Study." Cancers 2, no. 2: 420-435.