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Human brain tumour cell strains with deficient host-cell reactivation of N-methyl-N′-nitro-N-nitrosoguanidine-damaged adenovirus 5

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Abstract

HOST-CELL reactivation of a population of physically or chemically damaged viruses is said to occur when the plaque titre of the damaged (but not the control) virus population depends strongly on the cell strain selected to serve as the host to support virus growth1,2. Such cell strain-dependent differences in survival have classically been interpreted as reflecting known cellular differences in ability to repair DNA1,2. For example, we have previously demonstrated host-cell reactivation of UV-irradiated3 or benzo(a)pyrene diol-epoxide I (anti)-treated4 human adenoviruses. The survival of such treated virus populations is much greater when their plaque titre is measured using monolayers of fibroblasts with normal DNA repair than when using fibroblasts from patients having the genetic disease, xeroderma pigmentosum, which are deficient in repair of UV-damaged DNA. The work of Lytle and coworkers5,6 and Day3, using human cells, has shown host-cell reactivation of UV-damaged viruses to occur only when nuclear replicating DNA viruses are studied. To assess the hypothesis that human tumorigenesis is often associated with repair-deficient cells, we undertook a study of host-cell reactivation of various kinds of damage using human cell strains prepared both from tumours of different organs and from skin of people having genetic predisposition to, or familial occurrence of, cancer. As part of this work, we measured the survival of adenovirus 5 treated in vitro with the carcinogen N-methyl-N′-nitro-N-nitrosoguanidine (MNNG). We found that the use of cells from 4 of 13 human brain tumour strains as viral hosts resulted in less survival of the MNNG-damaged viruses than did the use of more than 20 other cell strains prepared from human tumours or from unaffected human organs (Fig. 1, Table 1). Previous studies have not detected abnormal DNA repair in human tumours7. We believe this to be the first report of host-cell reactivation of MNNG damage by mammalian cells.

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Authors and Affiliations

  1. Nucleic Acids Section, Laboratory of Molecular Carcinogenesis, CIP, DCCP, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, 20014

    RUFUS S. DAY III & CHUCK H. J. ZIOLKOWSKI

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  1. RUFUS S. DAY III
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  2. CHUCK H. J. ZIOLKOWSKI
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DAY, R., ZIOLKOWSKI, C. Human brain tumour cell strains with deficient host-cell reactivation of N-methyl-N′-nitro-N-nitrosoguanidine-damaged adenovirus 5. Nature 279, 797–799 (1979). https://doi.org/10.1038/279797a0

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  • DOI: https://doi.org/10.1038/279797a0

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