Enhancement of radiation damage in cellular DNA following unifilar substitution with iododeoxyuridine

Journal Article · Sat Mar 31 23:00:00 EST 1990 · International Journal of Radiation Oncology, Biology and Physics; (USA)

DOI:https://doi.org/10.1016/0360-3016(90)90410-L· OSTI ID:6973881

Fornace, Jr, A J; Dobson, P P; Kinsella, T J ^[1]

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1. National Cancer Institute, Bethesda, MD (USA)

The exact mechanism of x-ray radiosensitization with iododeoxyuridine (IdUrd) is not known. Using log phase V79 cells, we compared radiosensitization following unifilar (9 hr exposure) and bifilar (17 hr exposure) substitution with 10(-5) M IdUrd. The % thymidine replacement was 8% and 16%, respectively. Significant radiosensitization was found with unifilar (Do = 1.35 Gy, n = 5.8) and bifilar substitution (Do = 1.2 Gy, n = 4.0) compared to controls (Do = 1.7 Gy, n = 8.5). Using filter elution techniques, the enhancement ratios (ER) for double strand breaks (SB) were 1.5 and 2.0 for unifilar and bifilar substitution, respectively, whereas the enhancement ratio for single strand breaks were both greater than or equal to 2.1. Comparing the enhancement ratios with unifilar substitution for single strand breaks in substituted (2.4) and unsubstituted complement strands (1.9) as well as in unsubstituted duplex DNA (1.4) in cells containing IdUrd substituted DNA, there was increased damage in unsubstituted strands compared to irradiated controls. These data suggest that in vitro radiosensitization following unifilar substitution with IdUrd results, in part, from damage to unsubstituted complementary strand and adjacent doubly unsubstituted DNA. The radiolysis of halogenated DNA produces mobile reactive intermediates which may cause intermolecular DNA damage such as single strand breaks in unsubstituted DNA and resultant double strand breaks and this damage is probably responsible for increased lethality after x-irradiation.

• OSTI ID: 6973881
• Journal Information: International Journal of Radiation Oncology, Biology and Physics; (USA), Journal Name: International Journal of Radiation Oncology, Biology and Physics; (USA) Vol. 18:4; ISSN IOBPD; ISSN 0360-3016
• Country of Publication: United States
• Language: English

Related Subjects

560120* -- Radiation Effects on Biochemicals
Cells
& Tissue Culture
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
ANIMALS
ANTIMETABOLITES
AZINES
BIOLOGICAL EFFECTS
BIOLOGICAL RADIATION EFFECTS
DNA
DRUGS
ELECTROMAGNETIC RADIATION
GENETIC EFFECTS
GENETIC RADIATION EFFECTS
HAMSTERS
HETEROCYCLIC COMPOUNDS
HYDROXY COMPOUNDS
IODODEOXYURIDINE
IODOURACILS
IONIZING RADIATIONS
MAMMALS
NUCLEIC ACIDS
NUCLEOSIDES
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
ORGANIC IODINE COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PYRIMIDINES
RADIATION EFFECTS
RADIATIONS
RADIOINDUCTION
RADIOSENSITIVITY
RADIOSENSITIVITY EFFECTS
RIBOSIDES
RODENTS
STRAND BREAKS
SURVIVAL TIME
URACILS
VERTEBRATES
X RADIATION