Differential mutagen sensitivity of peripheral blood lymphocytes from smokers and nonsmokers: Effect of human cytomegalovirus infection

• Published in: Environmental and molecular mutagenesis Vol. 43; no. 3; pp. 169 - 178
• Main Authors: Albrecht, Thomas, Deng, Cheng Zong, Abdel-Rahman, Sherif Z., Fons, Michael, Cinciripini, Paul, El-Zein, Randa A.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 2004; Wiley-Liss
• Subjects: Adult; Antibiotics, Antineoplastic - toxicity; Biological and medical sciences; bleomycin; Bleomycin - toxicity; Case-Control Studies; Cells, Cultured; chromosome aberrations; Chromosome Aberrations - drug effects; Cytomegalovirus; Cytomegalovirus - physiology; Cytomegalovirus Infections - complications; Dose-Response Relationship, Drug; Female; Fundamental and applied biological sciences. Psychology; Genetics of eukaryotes. Biological and molecular evolution; Humans; Karyotyping; Lymphocytes - drug effects; Lymphocytes - virology; Male; Medical sciences; mutagen sensitivity; Mutagenicity Tests; Mutagens - pharmacology; smoking; Smoking - adverse effects; Toxicology; Chromosomal aberration; Antineoplastic agent; chromosome aberrations; Herpesviridae; Chromosome; Mutagen; Betaherpesvirinae; Blood; Human cytomegalovirus; Virus; Infection; Antibiotic; Sensitivity; Toxicology; Bleomycin; cytomegalovirus; Smoker; Genetics; mutagen sensitivity; Lymphocyte; Smoking
• ISSN: 0893-6692; 1098-2280
• DOI: 10.1002/em.20012

We used the mutagen sensitivity assay to test the hypothesis that human cytomegalovirus (HCMV) infection modifies the sensitivity of cells to genetic damage from genotoxic agents. Chromosome aberration (CA) frequency in peripheral blood lymphocytes (PBLs) from 20 smokers who were matched with 20 nonsmokers by age (± 5 years), sex, and ethnicity was evaluated following in vitro exposure to bleomycin and/or HCMV infection. Bleomycin induced significant (P < 0.05) concentration‐dependent increases in the frequency of aberrant cells, chromatid‐type damage (breaks), and chromosome‐type aberrations (deletions, rearrangements) in PBLs. The baseline (background) CA frequency was similar in both smokers and nonsmokers. Significantly higher frequencies of aberrant cells (P < 0.05) were observed in PBLs from smokers compared to nonsmokers at all bleomycin concentrations tested (10, 30 and 100 μg/ml). Infection of PBLs with HCMV induced a significant (P < 0.05) twofold increase in the frequency of CA (primarily chromatid breaks) in PBLs, regardless of the smoking status. PBLs from smokers and nonsmokers infected with HCMV prior to challenge with bleomycin demonstrated significant (P < 0.05) concentration‐dependent increases in the levels of aberrant cells, chromatid‐type damage (breaks), and chromosome‐type aberrations (deletions, rearrangements) compared to noninfected cells challenged with bleomycin. The frequency of induced CA was consistently higher for PBLs derived from smokers relative to nonsmokers (P = 0.06 and 0.002). These data indicate that, individually, both smoking and HCMV infection significantly enhance the sensitivity of PBLs to bleomycin‐induced genetic damage. More importantly, the data also suggest that smoking and HCMV infection interact synergistically to enhance the sensitivity of PBLs to such damage. Environ. Mol. Mutagen. 43:169–178, 2004. © 2004 Wiley‐Liss, Inc.