MOLECULAR RADIOBIOLOGY OF HUMAN CELL LINES

Thesis/Dissertation · Tue Jan 01 04:00:00 EST 1963

OSTI ID:4127160

Erikson, R L

Human tissue culture cells were sensitized to x-ray and ultraviolet light irradiation by culturing thein in medium containing equimolar (2 x 10/sup - 6/ M) concentrations of 5broinodeoxyuridine (BUdR), 5-chlorodeoxyuridine (CUdR), or 5-iododeoxyuridine (BUdR) plus 5-fluorodeoxyuridine to inhibit thymidylate synthesis. The increase in D/sub 37/ (dose required to kill 83% of the surviving cells on the stralghtline portion of the survivdl curve) was utilized to measure radiosensitivity. The sensitization factors (D/sub 37/ control cells/D/sub 37/ treated cells) for the cells were 1.6 (CUdR), 1.8 (BUdR), and 2.4 (IUdR) for x rays. The corresponding uv sensitization factors were 1.8, 10.0, and 2.0. IUdR was shown to be incorporated into DNA of cells grown in its presence by banding the isolated DNA in a Cs/sub 2/SO/sub 4/ density gradient. The increased density of this DNA can be related to the amount of IUdR incorporated. The labeling was compatible with a semi-conservative mode of DNA replication. The relationship between the radiosensitivity of cells and the extent of IUdR incorporation was deterinined for cells grown in medium containing different concentrations of IUdR. The x-ray sensitization factors were 1.0 (10/sup -8/ M IUdR), 1.2 (10/sup -7/ M), 1.6 (10/sup -6/ M), 2.8 (10/sup -6/ M) and 3.2 (5 x 10/sup -5/ M). IUdR incorporation and the sensitization factor increased with increasing concentration of IUdR in the medium. However, cell viability decreased sharply from 60% at 10/sup -5/ M to 6.0% at 5x 10/sup -5/ M IUdR. Two cell cultures were grown under conditions such that one contained IUdR incorporated into both strands of DNA while the other contained the same quantity of IUdR incorporated in only a single DNA strand. Both cultures displayed the saine radiosensitivity, indicating that the location of IUdR in the DNA molecule is unimportant, but that the total quantity incorporated deterinines the radiosensitivity of the cell. Glycerol present in the medium in which the cells are suspended for x irradiation caused a marked decrease in cell death. Glycerol protected BUdR- or IUdR-labeled cells to the same degree as control cells without eliininating the radiosensitization of an analogue. This indicates that the radiosensitization is and intrinsic cell property and is independent of the level of radiation protection. Experiinents were performed to compare radiosensitization of tissue culture celis and incorporation into DNA of 5-halogen derivatives of deoxyuridine (BUdR and IUdR) and deoxycytidine (BCdR and ICdR). Under identical conditions the deoxyuridine and deoxycytidine analogaes were incorporated to the same extent into DNA, producing about the same degree of radiosensitization. It was found that radiation resistance increased after the resumption of DNA synthesis in the period immediately after reinoval of the inhibitor, reaching a maximum just prior to division. After division the resistance of the cultures decressed, approaching that of an unsynchronized culture. (TCO)

• Research Organization: Originating Research Org. not identified
• NSA Number: NSA-18-003576
• OSTI ID: 4127160
• Country of Publication: Country unknown/Code not available
• Language: English

Related Subjects

ALCOHOLS
BIOCHEMISTRY
BIOLOGY AND MEDICINE
BROMINE COMPLEXES
CELL CULTURES
CESIUM SULFATES
CHLORINE COMPLEXES
CYTOLOGY
DENSITY
DEOXYURIDINE
FLUORINE COMPLEXES
GLYCERIN
IODINE COMPLEXES
MAN
MITOSIS
ORGANIC NITROGEN COMPOUNDS
RADIATION DOSES
RADIATION PROTECTION
RADIOSENSITIVITY
SUSPENSIONS
TISSUES
TOXICITY
ULTRAVIOLET RADIATION
X RADIATION