Induction of chromosome aberrations and mitotic arrest by cytomegalovirus in human cells
Human cytomegalovirus (CMV) is potentially an effective but often overlooked genotoxic agent in humans. We report here evidence that indicates that infection by CMV can induce chromosome alterations and mitotic inhibition. The frequency of chromosome aberrations induced was dependent on the input multiplicity of infection (m.o.i.) for human lung fibroblasts (LU), but not for human peripheral blood lymphocytes (PBLs) when both cell types were infected at the GO phase of the cell cycle. The aberrations induced by CMV were mostly chromatid breaks and chromosome pulverizations that resembled prematurely condensed S-phase chromatin. Pulverized chromosomes were not observed in LU cells infected with virus stocks that had been rendered nonlytic by UV-irradiation at 24,000 ergs/mm2 or from infection of human lymphocytes. In LU cells infected with UV-irradiated CMV, the frequency of aberrations induced was inversely dependent on the extent of the exposure of the CMV stock to the UV-light. In permissive CMV infection of proliferating LU cells at 24 hr after subculture, a high percentage (greater than 40%) of the metaphase cells were arrested at their first metaphase and displayed severely condensed chromosomes when harvested 48 hr later. A significant increase (p less than 0.05) in the chromosome aberration frequency was also observed. Our study shows that CMV infection is genotoxic to host cells. The types and extent of damage are dependent on the viral genome expression and on the cell cycle stage of the cells at the time of infection. The possible mechanisms for induction of chromosome damage by CMV are discussed.
- Research Organization:
- Univ. of Texas Medical Branch, Galveston (USA)
- OSTI ID:
- 6485860
- Journal Information:
- Environ. Mol. Mutagen.; (United States), Journal Name: Environ. Mol. Mutagen.; (United States) Vol. 12:4; ISSN EMMUE
- Country of Publication:
- United States
- Language:
- English
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63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
ANIMALS
BIOLOGICAL EFFECTS
BODY
CELL DIVISION
CELL PROLIFERATION
CHROMOSOMAL ABERRATIONS
CONNECTIVE TISSUE CELLS
ELECTROMAGNETIC RADIATION
FIBROBLASTS
GENETIC EFFECTS
LUNGS
MAMMALS
MAN
MICROORGANISMS
MITOSIS
MITOTIC INDEX
MUTATION FREQUENCY
MUTATIONS
ORGANS
PARASITES
PRIMATES
RADIATIONS
RESPIRATORY SYSTEM
SOMATIC CELLS
ULTRAVIOLET RADIATION
VERTEBRATES
VIRUSES