Dependence of the rate of DNA synthesis in x-irradiated HeLa S3 cells on dose and time after exposure

Journal Article · Sat Jan 01 04:00:00 EST 1977 · Radiat. Res.; (United States)

DOI:https://doi.org/10.2307/3574522· OSTI ID:7227738

Tolmach, L J; Jones, R W

After irradiation of randomly dividing cultures of HeLa S3 cells with 220-kV x rays, the rate of DNA synthesis, measured by pulsed incorporation of labeled thymidine, falls nearly exponentially with time (t/sub 1/2/ approximately 1.3 hr), in a dose-independent fashion. The fall is less rapid than that observed after addition of inhibitors of protein synthesis. With doses up to 8 krad, the rate reaches a minimum and begins to increase after 1-3 hr, the minima occurring at lower values and at slightly later times with increasing dose. The increase appears to be roughly linear for about 6 hr, with the slope an inverse function of dose in the range 1-8 krad. About 7-9 hr after the completion of irradiation, the rate again falls, although no more than 10 percent of the cells die sooner than 14 hr after irradiation with 8 krad (and later with smaller doses). Fluorodeoxyuridine-mediated delay in expression of the depression, described previously for doses up to 1 krad, occurs also at higher doses. During the period when the rate per culture rises, the rate in the individual cells, measured autoradiographically, appears to increase also, i.e., the rise presumably does not merely reflect populational shifts. The initial descending portion of the rate curve can be at least partially separated from the ascending portion by administering the total dose in suitably spaced fractions. If interpreted in terms of the model that attributes the initial depression in rate of synthesis to a temporary absence of replicon initiation, the results indicate that initiation is halted by an x-ray dose smaller than 1 krad; that it begins again after a dose-dependent delay amounting to about 0.7 hr after 1 krad and 1.5 hr after 7 krad; and that once begun, the rate of synthesis increases in a dose-dependent fashion. The second depression might derive from synchronization and/or from the imminence of cell death.

• Research Organization: Washington Univ., St. Louis
• OSTI ID: 7227738
• Journal Information: Radiat. Res.; (United States), Journal Name: Radiat. Res.; (United States) Vol. 69:1; ISSN RAREA
• Country of Publication: United States
• Language: English

Related Subjects

560121* -- Radiation Effects on Cells-- External Source-- (-1987)
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANTIMETABOLITES
ANTIMITOTIC DRUGS
AZINES
BIOLOGICAL EFFECTS
BIOLOGICAL RADIATION EFFECTS
BIOSYNTHESIS
CELL CULTURES
DNA
DOSE-RESPONSE RELATIONSHIPS
DRUGS
ELECTROMAGNETIC RADIATION
FLUOROURACILS
FUDR
HELA CELLS
HETEROCYCLIC COMPOUNDS
HYDROXY COMPOUNDS
IONIZING RADIATIONS
NUCLEIC ACIDS
NUCLEOSIDES
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC FLUORINE COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PROTEINS
PYRIMIDINES
RADIATION EFFECTS
RADIATIONS
RADIOSENSITIZERS
RESPONSE MODIFYING FACTORS
RIBOSIDES
SYNTHESIS
THYMIDINE
TIME DEPENDENCE
URACILS
X RADIATION