Involvement of DNA damage in hydroxyurea-mediated induction of endogenous murine retrovirus

Journal Article · Mon Apr 30 04:00:00 EDT 1979 · Virology; (United States)

DOI:https://doi.org/10.1016/0042-6822(79)90461-6· OSTI ID:6036482

Rascati, R J; Tennant, R W

Hydroxyurea (HU) induces AKR cells to produce endogenous murine retrovirus at a low frequency (approx. 1 x 10/sup -5/), and DNA synthesis is required soon after treatment with HU for induction to be observed (i.e., no stable induction intermediate is formed). Induction by HU can be enhanced by simultaneous treatment with halogenated pyrimidines, with the concomitant appearance of a stable induction intermediate state. The effects of the two compounds are synergistic, indicating an actual stimulation of HU-mediated induction by iodode-oxyuridine. Since HU inhibits semiconservative replication, and since (/sup 3/H)bromodeoxyuridine is incorporated into the cellular genome predominantly by unscheduled DNA synthesis (repair replication) under these conditions, this stimulation appears to be the result of insertion into DNA of the thymidine analogs during the repair of HU-induced alterations in the DNA. The nature of HU damage to DNA is not defined; if single-strand breaks are involved, they may occur at a frequency <10/sup -8/ and escape detection, but induction could also be due to other alterations in DNA. The characteristics of induction by HU, therefore, are similar to those of induction by other DNA-damaging treatments such as ..gamma.. or x irradiation or methylcholanthrene. This suggests that these agents may induce by similar, if not identical, mechanisms. Further, the ability of halogenated pyrimidines to form a stable induction intermediate when incorporated by repair synthesis, similar to the intermediate formed when the analogs are incorporated during semiconservative replication, suggests that the same sites are involved for induction by damaging agents or by halogenated pyrimidine incorporation.

• Research Organization: Oak Ridge National Lab., TN
• OSTI ID: 6036482
• Journal Information: Virology; (United States), Journal Name: Virology; (United States) Vol. 94:2; ISSN VIRLA
• Country of Publication: United States
• Language: English

Related Subjects

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63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
AMIDES
ANIMAL CELLS
ANIMALS
AZINES
BIOLOGICAL EFFECTS
BIOSYNTHESIS
DATA
DATA FORMS
DNA
EXPERIMENTAL DATA
HETEROCYCLIC COMPOUNDS
HYDROXY COMPOUNDS
HYDROXYUREA
INFORMATION
ISOLATED VALUES
MAMMALS
MICE
MICROORGANISMS
NUCLEIC ACIDS
NUMERICAL DATA
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PARASITES
PYRIMIDINES
RODENTS
SYNTHESIS
VERTEBRATES
VIRUSES