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

Thomas Albrecht, Cheng Zong Deng, Sherif Z. Abdel-Rahman, Michael Fons, Paul Cinciripini, Randa A. El-Zein

    Research output: Contribution to journalArticlepeer-review

    21 Scopus citations

    Abstract

    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 date also suggest that smoking and HCMV infection interact synergistically to enhance the sensitivity of PBLs to such damage. Environ. Mol. Mutagen.

    Original languageEnglish (US)
    Pages (from-to)169-178
    Number of pages10
    JournalEnvironmental and Molecular Mutagenesis
    Volume43
    Issue number3
    DOIs
    StatePublished - 2004

    Keywords

    • Bleomycin
    • Chromosome aberrations
    • Cytomegalovirus
    • Mutagen sensitivity
    • Smoking

    ASJC Scopus subject areas

    • Epidemiology
    • Genetics(clinical)
    • Health, Toxicology and Mutagenesis

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